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Sample records for pcbs alter dopamine

  1. PCBs Alter Dopamine Mediated Function in Aging Workers

    Science.gov (United States)

    2011-01-01

    PCBs Alter Dopamine Mediated Function in Aging Workers 5a. CONTRACT NUMBER 5b. GRANT NUMBER DAMD17-02-1-0173 5c. PROGRAM ELEMENT...hypothesized that occupational exposure to polychlorinated biphenyls (PCBs) reduces dopamine (DA) terminal densities in the basal ganglia. We found...motor function in women compared to similarly aged men with similar bone lead levels. These latter findings are the first to demonstrate a sexual

  2. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

    Directory of Open Access Journals (Sweden)

    James P. Kesby

    2013-07-01

    Full Text Available Schizophrenia is a heterogeneous group of disorders with unknown aetiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesised that abnormal dopamine signalling in the adult patient may result from altered dopamine signalling during foetal brain development. Environmental and genetic risk factors can be modelled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the aetiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD deficiency. DVD-deficient adult rats display an altered behavioural profile in response to dopamine releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters dopamine metabolism in the developing brain. We speculate such alterations in foetal brain development may change the trajectory of dopamine neuron ontogeny to induce the behavioural abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in dopamine ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  3. Research Review: Dopamine Transfer Deficit: A Neurobiological Theory of Altered Reinforcement Mechanisms in ADHD

    Science.gov (United States)

    Tripp, Gail; Wickens, Jeff R.

    2008-01-01

    This review considers the hypothesis that changes in dopamine signalling might account for altered sensitivity to positive reinforcement in children with ADHD. The existing evidence regarding dopamine cell activity in relation to positive reinforcement is reviewed. We focus on the anticipatory firing of dopamine cells brought about by a transfer…

  4. Fatty acid alterations caused by PCBs (Aroclor 1242) and copper in adipose tissue around lymph nodes of mink

    International Nuclear Information System (INIS)

    Kaekelae, R.; Hyvaerinen, H.

    1999-01-01

    Fatty acid composition was determined in adipose tissue surrounding the mesenteric lymph nodes of mink (Mustela vison) exposed to polychlorinated biphenyls (PCBs: 1 mg Aroclor 1242 in food day -1 for 28 days) and/or copper (62 mg kg -1 food). These specific adipose tissues are known to have functional relationships with lymphocytes, and proliferation of cultured lymphocytes is influenced by the quality of fatty acids available in media. In six experimental groups the diet was based on freshwater fish, and in two groups it was based on marine fish. These basal diets differed in terms of fatty acid composition and content of fat-soluble vitamins A 1 and E. The fatty acid composition of membrane phospholipids (PL) responded to PCBs more than that of triacylglycerols (TG). The effects of copper were small. In female minks fed a diet of freshwater fish, the proportion of highly unsaturated fatty acids in PL decreased by 5 wt.% due to PCBs, and the acids seemed to be replaced by monounsaturated fatty acids (9 wt.% increase of total). This decrease of highly unsaturated fatty acids in PL was milder in minks on the marine fish diet rich in fat-soluble vitamins. In TG of minks on the marine diet, however, PCBs decreased the proportion of docosahexaenoic acid (22:6n-3). The possibility that these alterations in the fatty acid metabolism of adipose tissue supporting the lymph nodes affect immune function during PCB exposure should be studied further. Interestingly, the quality of the fish diet affected the magnitude of the alterations. The fatty acid responses may also differ between males and females. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. Altered effect of dopamine transporter 3'UTR VNTR genotype on prefrontal and striatal function in schizophrenia.

    Science.gov (United States)

    Prata, Diana P; Mechelli, Andrea; Picchioni, Marco M; Fu, Cynthia H Y; Toulopoulou, Timothea; Bramon, Elvira; Walshe, Muriel; Murray, Robin M; Collier, David A; McGuire, Philip

    2009-11-01

    The dopamine transporter plays a key role in the regulation of central dopaminergic transmission, which modulates cognitive processing. Disrupted dopamine function and impaired executive processing are robust features of schizophrenia. To examine the effect of a polymorphism in the dopamine transporter gene (the variable number of tandem repeats in the 3' untranslated region) on brain function during executive processing in healthy volunteers and patients with schizophrenia. We hypothesized that this variation would have a different effect on prefrontal and striatal activation in schizophrenia, reflecting altered dopamine function. Case-control study. Psychiatric research center. Eighty-five subjects, comprising 44 healthy volunteers (18 who were 9-repeat carriers and 26 who were 10-repeat homozygotes) and 41 patients with DSM-IV schizophrenia (18 who were 9-repeat carriers and 23 who were 10-repeat homozygotes). Regional brain activation during word generation relative to repetition in an overt verbal fluency task measured by functional magnetic resonance imaging. Main effects of genotype and diagnosis on activation and their interaction were estimated with analysis of variance in SPM5. Irrespective of diagnosis, the 10-repeat allele was associated with greater activation than the 9-repeat allele in the left anterior insula and right caudate nucleus. Trends for the same effect in the right insula and for greater deactivation in the rostral anterior cingulate cortex were also detected. There were diagnosis x genotype interactions in the left middle frontal gyrus and left nucleus accumbens, where the 9-repeat allele was associated with greater activation than the 10-repeat allele in patients but not controls. Insular, cingulate, and striatal function during an executive task is normally modulated by variation in the dopamine transporter gene. Its effect on activation in the dorsolateral prefrontal cortex and ventral striatum is altered in patients with schizophrenia

  6. Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms

    Science.gov (United States)

    dela Peña, Ike; Gevorkiana, Ruzanna; Shi, Wei-Xing

    2015-01-01

    The precise mechanisms by which cocaine and amphetamine-like psychostimulants exert their reinforcing effects are not yet fully defined. It is widely believed, however, that these drugs produce their effects by enhancing dopamine neurotransmission in the brain, especially in limbic areas such as the nucleus accumbens, by inducing dopamine transporter-mediated reverse transport and/or blocking dopamine reuptake though the dopamine transporter. Here, we present the evidence that aside from dopamine transporter, non-dopamine transporter-mediated mechanisms also participate in psychostimulant-induced dopamine release and contribute to the behavioral effects of these drugs, such as locomotor activation and reward. Accordingly, psychostimulants could increase norepinephrine release in the prefrontal cortex, the latter then alters the firing pattern of dopamine neurons resulting in changes in action potential-dependent dopamine release. These alterations would further affect the temporal pattern of dopamine release in the nucleus accumbens, thereby modifying information processing in that area. Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or inhibited by dopamine depending on its temporal relationship to dopamine release. Specific temporal patterns of dopamine release may also be required for certain forms of synaptic plasticity in the nucleus accumbens. Together, these effects induced by psychostimulants, mediated through a non-dopamine transporter-mediated mechanism involving norepinephrine and the prefrontal cortex, may also contribute importantly to the reinforcing properties of these drugs. PMID:26209364

  7. Altered neurocircuitry in the dopamine transporter knockout mouse brain.

    Directory of Open Access Journals (Sweden)

    Xiaowei Zhang

    2010-07-01

    Full Text Available The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI. Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn(2+ into the prefrontal cortex indicated that DAT KO mice have a truncated Mn(2+ distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn(2+ transport into more posterior midbrain nuclei and contralateral

  8. Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease

    International Nuclear Information System (INIS)

    Bennett, J.P. Jr.; Wooten, G.F.

    1986-01-01

    Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H-spiperone ( 3 H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3 H-SP in dopamine-denervated compared with intact striata. 3 H-SP in vivo binds to less than 10% of striatal sites labeled by 3 H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo

  9. PINK1 heterozygous mutations induce subtle alterations in dopamine-dependent synaptic plasticity

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    Madeo, G.; Schirinzi, T.; Martella, G.; Latagliata, E.C.; Puglisi, F.; Shen, J.; Valente, E.M.; Federici, M.; Mercuri, N.B.; Puglisi-Allegra, S.; Bonsi, P.; Pisani, A.

    2014-01-01

    Background Homozygous or compound heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene are causative of autosomal recessive, early onset PD. Single heterozygous mutations have been repeatedly detected in a subset of patients as well as in non-affected subjects, and their significance has long been debated. Several neurophysiological studies from non-manifesting PINK1 heterozygotes have shown the existence of neural plasticity abnormalities, indicating the presence of specific endophenotypic traits in the heterozygous state. Methods In the present study, we performed a functional analysis of corticostriatal synaptic plasticity in heterozygous PINK1 knock-out (PINK1+/−) mice by a multidisciplinary approach. Results We found that, despite a normal motor behavior, repetitive activation of cortical inputs to striatal neurons failed to induce long-term potentiation (LTP), whereas long-term depression (LTD) was normal. Although nigral dopaminergic neurons exhibited normal morphological and electrophysiological properties with normal responses to dopamine receptor activation, we measured a significantly lower dopamine release in the striatum of PINK1+/−, compared to control mice, suggesting that a decrease in stimulus-evoked dopamine overflow acts as a major determinant for the LTP deficit. Accordingly, pharmacological agents capable of increasing the availability of dopamine in the synaptic cleft restored a normal LTP in heterozygous mice. Moreover, MAO-B inhibitors rescued a physiological LTP and a normal dopamine release. Conclusions Our results provide novel evidence for striatal plasticity abnormalities even in the heterozygous disease state. These alterations might be considered an endophenotype to this monogenic form of PD, and a valid tool to characterize early disease stage and design possible disease-modifying therapies. PMID:24167038

  10. High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity.

    Science.gov (United States)

    Meyers, Allison M; Mourra, Devry; Beeler, Jeff A

    2017-01-01

    The contribution of high fructose corn syrup (HFCS) to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO) and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6) received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets.

  11. High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity.

    Directory of Open Access Journals (Sweden)

    Allison M Meyers

    Full Text Available The contribution of high fructose corn syrup (HFCS to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6 received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets.

  12. Investigation of PCBs biodegradation by soil bacteria using tritium-labeled PCBs

    International Nuclear Information System (INIS)

    Kim, A.A.; Djuraeva, G.T.; Takhtobin, K.S.; Kadirova, M.; Yadgarov, H.T.; Zinovev, P.V.; Abdukarimov, A.A.

    2004-01-01

    The method of tritium labeling of polychlorinated biphenyls (PCBs) has been developed. It allows producing of uniformly labeled tritium PCBs. High specific activity permits the tracing all of the tritium labeled PCBs biodegradation products. Radiochemical approach of the investigation of PCBs microbial degradation has been developed and PCB-destructive activity of soil bacteria strains has been studied. It was found that 4 investigated bacteria strains of Bacillus sp. has the ability accumulate and destroy PCBs. Use of developed radiochemical methods in complex with other analytical methods in investigation of PCBs biodegradation provide useful additional information. The radiochemical methods developed can be successfully used for wide screening of microorganisms, destructors of PCBs. (author)

  13. Biotransformation of polychlorinated biphenyls (PCBs) and bioformation of hydroxylated PCBs in fish

    Energy Technology Data Exchange (ETDEWEB)

    Buckman, Andrea H. [Department of Environmental Biology, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); National Waters Research Institute, Environment Canada, Burlington, Ont., Canada L7R 4A6 (Canada); Wong, Charles S. [Department of Chemistry, University of Alberta, Edmonton, Alta. (Canada); Chow, Elaine A. [Department of Chemistry, University of Alberta, Edmonton, Alta. (Canada); Brown, Scott B. [National Waters Research Institute, Environment Canada, Burlington, Ont., L7R 4A6 (Canada); Solomon, Keith R. [Department of Environmental Biology, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Fisk, Aaron T. [Warnell School of Forest Resources, University of Georgia, Athens, GA 30602-2152 (United States)]. E-mail: afisk@smokey.forestry.uga.edu

    2006-06-15

    Hydroxylated PCBs (OH-PCBs) are a class of organic contaminants that have been found recently in the plasma of Great Lakes fish, the source of which is either bioformation from PCBs or accumulation from the environment. To address the potential for fish to biotransform PCBs and bioform OH-PCBs juvenile rainbow trout (Oncorhynchus mykiss; {approx}80 g) were exposed to dietary concentrations of an environmentally relevant mixture of PCBs. Eight OH-PCBs were found in the plasma of rainbow trout after 30 days of exposure to the PCBs, the relative pattern of which was similar to those observed in wild lake trout (Salvelinus namaycush) from Lake Ontario. Hydroxylated-PCBs were not found (detection limit 0.02 pg/g) in the food or control (not PCB-exposed) fish. A curvilinear log t {sub 1/2}-log K {sub ow} relationship for recalcitrant PCBs was found, similar to previously reported relationships, although t {sub 1/2} values were longer and shorter than studies using smaller fish or cooler temperatures, respectively. A number of PCB congeners fell below the log t {sub 1/2}-log K {sub ow} relationship providing the first estimates of non-chiral PCB biotransformation rates in fish. Enantioselective degradation of the chiral congeners PCBs 91 and 136, also indicated biotransformation. Biotransformation of PCBs was structure-dependent with greater biotransformation of PCBs with vicinal hydrogen atoms in the meta/para positions, suggesting CYP 2B-like biotransformation. Other chiral congeners with a meta/para substitution pattern showed no enantioselective degradation but were biotransformed based on the log t {sub 1/2}-log K {sub ow} relationship. The results of this study demonstrate that laboratory held rainbow trout can biotransform a number of PCB congeners and that bioformation is likely an important source of OH-PCBs in wild salmonids of the Great Lakes.

  14. Biotransformation of polychlorinated biphenyls (PCBs) and bioformation of hydroxylated PCBs in fish

    International Nuclear Information System (INIS)

    Buckman, Andrea H.; Wong, Charles S.; Chow, Elaine A.; Brown, Scott B.; Solomon, Keith R.; Fisk, Aaron T.

    2006-01-01

    Hydroxylated PCBs (OH-PCBs) are a class of organic contaminants that have been found recently in the plasma of Great Lakes fish, the source of which is either bioformation from PCBs or accumulation from the environment. To address the potential for fish to biotransform PCBs and bioform OH-PCBs juvenile rainbow trout (Oncorhynchus mykiss; ∼80 g) were exposed to dietary concentrations of an environmentally relevant mixture of PCBs. Eight OH-PCBs were found in the plasma of rainbow trout after 30 days of exposure to the PCBs, the relative pattern of which was similar to those observed in wild lake trout (Salvelinus namaycush) from Lake Ontario. Hydroxylated-PCBs were not found (detection limit 0.02 pg/g) in the food or control (not PCB-exposed) fish. A curvilinear log t 1/2 -log K ow relationship for recalcitrant PCBs was found, similar to previously reported relationships, although t 1/2 values were longer and shorter than studies using smaller fish or cooler temperatures, respectively. A number of PCB congeners fell below the log t 1/2 -log K ow relationship providing the first estimates of non-chiral PCB biotransformation rates in fish. Enantioselective degradation of the chiral congeners PCBs 91 and 136, also indicated biotransformation. Biotransformation of PCBs was structure-dependent with greater biotransformation of PCBs with vicinal hydrogen atoms in the meta/para positions, suggesting CYP 2B-like biotransformation. Other chiral congeners with a meta/para substitution pattern showed no enantioselective degradation but were biotransformed based on the log t 1/2 -log K ow relationship. The results of this study demonstrate that laboratory held rainbow trout can biotransform a number of PCB congeners and that bioformation is likely an important source of OH-PCBs in wild salmonids of the Great Lakes

  15. Use of tritium-labeled PCBs for investigation of PCBs biodegradation by soil bacteria

    International Nuclear Information System (INIS)

    Kim, A.A.; Djuraeva, G.T.; Takhtobiri, K.S.; Yadgarov, H.T.; Zinovev, P. V.; Abdukarimov, A.A.

    2002-01-01

    The method for tritium labelling of polychlorinated biphenyls (PCBs) was developed. The strains of soil bacteria - destructors of chloro organic compounds was studied with the help of test-system based on the using of tritium-labeled PCBs. The strains of bacteria were grown on the agar synthetic medium and then were introduced into the synthetic medium containing tritium-labeled mixture of PCBs (commercial mark - SOVOL) as alone source of carbon. The samples were analysed after one and two months period of incubation. PCBs were extracted by hexane from fraction of bacteria and fraction of cultural medium and radioactivity was measured. The samples were analyzed by thin layer chromatography (TLC) with following radioautography. Additionally samples were analyzed by gas chromatography. It was found that all selected strains survived in the medium with PCBs as alone source of carbon and bacteria accumulated PCBs from cultural medium. Accumulation of PCBs by strains of bacteria was different. The TLC analysis detected additional compounds labeled by tritium, that prove the degradation of PCBs in presence of bacteria. The gas chromatography analysis of cultural medium and bacteria detected redistribution in the system and qualitative changes of PCBs in bacteria. The strains of bacteria also were grown in model condition on the soil with tritium labeled PCBs. We found that some strains effectively destroy PCBs with decreasing level of tritium label in the soil. The using of tritium labeled PCBs' allows to introduce precise quantitative characteristics for study of accumulation and biodegradation PCBs by soil bacteria strains. Developed test-system is very useful tool for selection of new strains of soil bacteria - destructors of PCBs

  16. Dopamine Release and Uptake Impairments and Behavioral Alterations Observed in Mice that Model Fragile X Mental Retardation Syndrome.

    Science.gov (United States)

    Fulks, Jenny L; O'Bryhim, Bliss E; Wenzel, Sara K; Fowler, Stephen C; Vorontsova, Elena; Pinkston, Jonathan W; Ortiz, Andrea N; Johnson, Michael A

    2010-10-20

    In this study we evaluated the relationship between amphetamine-induced behavioral alterations and dopamine release and uptake characteristics in Fmr1 knockout (Fmr1 KO) mice, which model fragile X syndrome. The behavioral analyses, obtained at millisecond temporal resolution and 2 mm spatial resolution using a force-plate actometer, revealed that Fmr1 KO mice express a lower degree of focused stereotypy compared to wild type (WT) control mice after injection with 10 mg/kg (ip) amphetamine. To identify potentially related neurochemical mechanisms underlying this phenomenon, we measured electrically-evoked dopamine release and uptake using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in striatal brain slices. At 10 weeks of age, dopamine release per pulse, which is dopamine release corrected for differences in uptake, was unchanged. However, at 15 (the age of behavioral testing) and 20 weeks of age, dopamine per pulse and the maximum rate of dopamine uptake was diminished in Fmr1 KO mice compared to WT mice. Dopamine uptake measurements, obtained at different amphetamine concentrations, indicated that dopamine transporters in both genotypes have equal affinities for amphetamine. Moreover, dopamine release measurements from slices treated with quinpirole, a D2-family receptor agonist, rule out enhanced D2 autoreceptor sensitivity as a mechanism of release inhibition. However, dopamine release, uncorrected for uptake and normalized against the corresponding pre-drug release peaks, increased in Fmr1 KO mice, but not in WT mice. Collectively, these data are consistent with a scenario in which a decrease in extracellular dopamine levels in the striatum result in diminished expression of focused stereotypy in Fmr1 KO mice.

  17. Pyrethroid pesticide-induced alterations in dopamine transporter function

    International Nuclear Information System (INIS)

    Elwan, Mohamed A.; Richardson, Jason R.; Guillot, Thomas S.; Caudle, W. Michael; Miller, Gary W.

    2006-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal dopaminergic pathway. Several epidemiological studies have demonstrated an association between pesticide exposure and the incidence of PD. Studies from our laboratory and others have demonstrated that certain pesticides increase levels of the dopamine transporter (DAT), an integral component of dopaminergic neurotransmission and a gateway for dopaminergic neurotoxins. Here, we report that repeated exposure (3 injections over 2 weeks) of mice to two commonly used pyrethroid pesticides, deltamethrin (3 mg/kg) and permethrin (0.8 mg/kg), increases DAT-mediated dopamine uptake by 31 and 28%, respectively. Using cells stably expressing DAT, we determined that exposure (10 min) to deltamethrin and permethrin (1 nM-100 μM) had no effect on DAT-mediated dopamine uptake. Extending exposures to both pesticides for 30 min (10 μM) or 24 h (1, 5, and 10 μM) resulted in significant decrease in dopamine uptake. This reduction was not the result of competitive inhibition, loss of DAT protein, or cytotoxicity. However, there was an increase in DNA fragmentation, an index of apoptosis, in cells exhibiting reduced uptake at 30 min and 24 h. These data suggest that up-regulation of DAT by in vivo pyrethroid exposure is an indirect effect and that longer-term exposure of cells results in apoptosis. Since DAT can greatly affect the vulnerability of dopamine neurons to neurotoxicants, up-regulation of DAT by deltamethrin and permethrin may increase the susceptibility of dopamine neurons to toxic insult, which may provide insight into the association between pesticide exposure and PD

  18. Single cocaine exposure does not alter striatal pre-synaptic dopamine function in mice: an [18 F]-FDOPA PET study.

    Science.gov (United States)

    Bonsall, David R; Kokkinou, Michelle; Veronese, Mattia; Coello, Christopher; Wells, Lisa A; Howes, Oliver D

    2017-12-01

    Cocaine is a recreational drug of abuse that binds to the dopamine transporter, preventing reuptake of dopamine into pre-synaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and post-synaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on pre-synaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography have revealed impaired pre-synaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use micro positron emission tomography imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of pre-synaptic dopamine function. We show that a dose of 20 mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (KiCer: 0.0097 per min vs. 0.0112 per min in vehicle controls, p > 0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p > 0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to pre-synaptic dopaminergic neurons are not initiated following a single exposure to the drug. © 2017 International Society for Neurochemistry.

  19. PCBs in various Schools

    Science.gov (United States)

    Characterize primary and secondary sources of PCBs in school buildings Characterize levels of PCBs in air, dust, soil and on surfaces; investigate relationships between sources and environmental levels Apply an exposure model for estimating children’s exposures to PCBs in schools...

  20. Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

    Science.gov (United States)

    Rukavina Mikusic, Natalia L; Kouyoumdzian, Nicolás M; Del Mauro, Julieta S; Cao, Gabriel; Trida, Verónica; Gironacci, Mariela M; Puyó, Ana M; Toblli, Jorge E; Fernández, Belisario E; Choi, Marcelo R

    2018-01-01

    Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na + , K + -ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Altered dopamine signaling in naturally occurring maternal neglect.

    Directory of Open Access Journals (Sweden)

    Stephen C Gammie

    2008-04-01

    Full Text Available Child neglect is the most common form of child maltreatment, yet the biological basis of maternal neglect is poorly understood and a rodent model is lacking.The current study characterizes a population of mice (MaD1 which naturally exhibit maternal neglect (little or no care of offspring at an average rate of 17% per generation. We identified a set of risk factors that can predict future neglect of offspring, including decreased self-grooming and elevated activity. At the time of neglect, neglectful mothers swam significantly more in a forced swim test relative to nurturing mothers. Cross-fostered offspring raised by neglectful mothers in turn exhibit increased expression of risk factors for maternal neglect and decreased maternal care as adults, suggestive of possible epigenetic contributions to neglect. Unexpectedly, offspring from neglectful mothers elicited maternal neglect from cross-fostered nurturing mothers, suggesting that factors regulating neglect are not solely within the mother. To identify a neurological pathway underlying maternal neglect, we examined brain activity in neglectful and nurturing mice. c-Fos expression was significantly elevated in neglectful relative to nurturing mothers in the CNS, particularly within dopamine associated areas, such as the zona incerta (ZI, ventral tegmental area (VTA, and nucleus accumbens. Phosphorylated tyrosine hydroxylase (a marker for dopamine production was significantly elevated in ZI and higher in VTA (although not significantly in neglectful mice. Tyrosine hydroxylase levels were unaltered, suggesting a dysregulation of dopamine activity rather than cell number. Phosphorylation of DARPP-32, a marker for dopamine D1-like receptor activation, was elevated within nucleus accumbens and caudate-putamen in neglectful versus nurturing dams.These findings suggest that atypical dopamine activity within the maternal brain, especially within regions involved in reward, is involved in naturally

  2. Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

    Science.gov (United States)

    Siciliano, Cody A.; Fordahl, Steve C.

    2016-01-01

    , the dopamine transporter (DAT). Preclinical literature has shown that reduced cocaine potency at the DAT increases cocaine taking, highlighting the key role of tolerance in addiction. Addiction is characterized by cycles of abstinence, often for many months, followed by relapse, making it important to determine possible interactions between abstinence and subsequent drug re-exposure. Using a rodent model of cocaine abuse, we found long-lasting, possibly permanent, cocaine-induced alterations to the DAT, whereby cocaine tolerance is reinstated by minimal drug exposure, even after recovery of DAT function over prolonged abstinence periods. PMID:27466327

  3. Altered dopamine levels induced by the parasite Profilicollis antarcticus on its intermediate host, the crab Hemigrapsus crenulatus

    Directory of Open Access Journals (Sweden)

    JOSÉ MIGUEL ROJAS

    2005-01-01

    Full Text Available A serotonergic pathway is apparently involved in parasite-host interactions. Previous studies conducted in our laboratory showed increased rates in oxygen consumption and alterations in body posture in the crab Hemigrapsus crenulatus parasitized by the acanthocephalan, Profilicollis antarcticus. Such changes may be related to the functions described for biogenic amines in crustaceans. During the infective stage the acanthocephalans live freely in the hemocelomic cavity, suggesting that the possible alteration induced by biogenic amines may be related to their neurohormonal function in crustaceans. To test whether the presence of P. antarcticus produced neurohormonal changes in its intermediate host, H. crenulatus, we analyzed serotonin and dopamine levels in the host using HPLC with electrochemical detection. Two groups of 11 female crabs were studied; one group was artificially inoculated with two cystacanths while the other was used as the control. Our results show a dramatic increase in hemolymph dopamine, but not serotonin in H. crenulatus parasitized by the acanthocephalan P. antarcticus. Our results, along with those reported by Maynard (1996, suggest a parasite-specific strategy involved in the behavior alteration caused by the acanthocephalans on their intermediate host. The use of a biogenic amine as a mechanism of interaction by the parasites gives them an endless number of alternative potential actions on their intermediate hosts

  4. Altered dopamine levels induced by the parasite Profilicollis antarcticus on its intermediate host, the crab Hemigrapsus crenulatus.

    Science.gov (United States)

    Rojas, José Miguel; Ojeda, F Patricio

    2005-01-01

    A serotonergic pathway is apparently involved in parasite-host interactions. Previous studies conducted in our laboratory showed increased rates in oxygen consumption and alterations in body posture in the crab Hemigrapsus crenulatus parasitized by the acanthocephalan, Profilicollis antarcticus. Such changes may be related to the functions described for biogenic amines in crustaceans. During the infective stage the acanthocephalans live freely in the hemocelomic cavity, suggesting that the possible alteration induced by biogenic amines may be related to their neurohormonal function in crustaceans. To test whether the presence of P. antarcticus produced neurohormonal changes in its intermediate host, H. crenulatus, we analyzed serotonin and dopamine levels in the host using HPLC with electrochemical detection. Two groups of 11 female crabs were studied; one group was artificially inoculated with two cystacanths while the other was used as the control. Our results show a dramatic increase in hemolymph dopamine, but not serotonin in H. crenulatus parasitized by the acanthocephalan P. antarcticus. Our results, along with those reported by Maynard (1996), suggest a parasite-specific strategy involved in the behavior alteration caused by the acanthocephalans on their intermediate host. The use of a biogenic amine as a mechanism of interaction by the parasites gives them an endless number of alternative potential actions on their intermediate hosts.

  5. Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution*

    Science.gov (United States)

    Nishi, Akinori; Matamales, Miriam; Musante, Veronica; Valjent, Emmanuel; Kuroiwa, Mahomi; Kitahara, Yosuke; Rebholz, Heike; Greengard, Paul; Girault, Jean-Antoine; Nairn, Angus C.

    2017-01-01

    The interaction of glutamate and dopamine in the striatum is heavily dependent on signaling pathways that converge on the regulatory protein DARPP-32. The efficacy of dopamine/D1 receptor/PKA signaling is regulated by DARPP-32 phosphorylated at Thr-34 (the PKA site), a process that inhibits protein phosphatase 1 (PP1) and potentiates PKA action. Activation of dopamine/D1 receptor/PKA signaling also leads to dephosphorylation of DARPP-32 at Ser-97 (the CK2 site), leading to localization of phospho-Thr-34 DARPP-32 in the nucleus where it also inhibits PP1. In this study the role of glutamate in the regulation of DARPP-32 phosphorylation at four major sites was further investigated. Experiments using striatal slices revealed that glutamate decreased the phosphorylation states of DARPP-32 at Ser-97 as well as Thr-34, Thr-75, and Ser-130 by activating NMDA or AMPA receptors in both direct and indirect pathway striatal neurons. The effect of glutamate in decreasing Ser-97 phosphorylation was mediated by activation of PP2A. In vitro phosphatase assays indicated that the PP2A/PR72 heterotrimer complex was likely responsible for glutamate/Ca2+-regulated dephosphorylation of DARPP-32 at Ser-97. As a consequence of Ser-97 dephosphorylation, glutamate induced the nuclear localization in cultured striatal neurons of dephospho-Thr-34/dephospho-Ser-97 DARPP-32. It also reduced PKA-dependent DARPP-32 signaling in slices and in vivo. Taken together, the results suggest that by inducing dephosphorylation of DARPP-32 at Ser-97 and altering its cytonuclear distribution, glutamate may counteract dopamine/D1 receptor/PKA signaling at multiple cellular levels. PMID:27998980

  6. Early social deprivation impairs pair bonding and alters serum corticosterone and the NAcc dopamine system in mandarin voles.

    Science.gov (United States)

    Yu, Peng; An, Shucheng; Tai, Fadao; Wang, Jianli; Wu, Ruiyong; Wang, Bo

    2013-12-01

    Early life stress has a long-term negative impact on emotion, learning, memory and adult sexual behavior, and these deficits most likely impair pair bonding. Here, we investigated whether early social deprivation (ED) affects the formation of pair bonds in socially monogamous mandarin voles (Microtus mandarinus). In a partner preference test (PPT), ED-reared adult females and males did not show a preference for their partner, spent more time exploring the cage of an unfamiliar animal and directed high levels of aggression toward unfamiliar animals. In social interaction test, ED increased exploring behavior only in females, but increased movement around the partner and reduced inactivity in both males and females. Three days of cohabitation did not alter serum corticosterone levels in ED-reared males, but increased corticosterone levels in males that received bi-parental care (PC). Interestingly, serum corticosterone levels in ED- and PC-reared females declined after cohabitation. ED significantly increased basal serum corticosterone levels in males, but had no effect on females. ED significantly up-regulated the levels of dopamine and the mRNA expression of dopamine 1-type receptor (D1R) in the nucleus accumbens (NAcc) in females and males. ED suppressed dopamine 2-type receptor mRNA (D2R) expression in females, but increased this in males. After three days of cohabitation, levels of D1R mRNA and D2R mRNA expression changed in opposite directions in PC-reared voles, but in the same direction in ED-reared males, and only the expression of D2R mRNA increased in ED-reared females. Our results indicate that early social deprivation inhibits pair bonding at adulthood. This inhibition is possibly associated with sex-specific alterations in serum corticosterone, levels of dopamine and mRNA expression of two types of dopamine receptors in the NAcc. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Suppression of serotonin hyperinnervation does not alter the dysregulatory influences of dopamine depletion on striatal neuropeptide gene expression in rodent neonates.

    Science.gov (United States)

    Basura, G J; Walker, P D

    1999-10-15

    Sixty days following neonatal dopamine depletion (>98%) with 6-hydroxydopamine, preprotachykinin and preprodynorphin mRNA levels were significantly reduced (67 and 78% of vehicle controls, respectively) in the anterior striatum as determined by in situ hybridization while preproenkephalin mRNA expression was elevated (133% of vehicle controls). Suppression of the serotonin hyperinnervation phenomenon in the dopamine-depleted rat with 5,7-dihydroxytryptamine yielded no significant alterations in reduced striatal preprotachykinin (66%) or preprodynorphin (64%) mRNA levels, while preproenkephalin mRNA expression remained significantly elevated (140%). These data suggest that striatal serotonin hyperinnervation does not contribute to the development of dysregulated striatal neuropeptide transmission in either direct or indirect striatal output pathways following neonatal dopamine depletion.

  8. Polychlorinated dioxins, furans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs) and indicator PCBs (ind-PCBs) in egg and egg products in Turkey.

    Science.gov (United States)

    Olanca, Burcu; Cakirogullari, Gul Celik; Ucar, Yunus; Kirisik, Dursun; Kilic, Devrim

    2014-01-01

    The aim of the study is to determine concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs) and indicator PCBs (ind-PCBs) in eggs from cage hens without soil contact, pasteurized egg samples and imported egg yolk powder samples in Turkey. Concentrations of PCDD/Fs, PCDD/Fs and dl-PCBs, and ind-PCBs in eggs and pasteurized egg samples are in the range of 0.247-1.527 pg WHO-TEQ(2005)g(-1) fat, 0.282-1.762 pg WHO-TEQ(2005)g(-1) fat and 202-1,235 pg g(-1) fat, respectively. For egg yolk powder samples, concentrations of PCDD/Fs, PCDD/Fs and dl-PCBs, and ind-PCBs are in the range of 0.122-0.494 pg WHO-TEQ(2005)g(-1) fat, 0.214-0.640 pg WHO-TEQ(2005)g(-1) fat and 217-1,498 pg g(-1) fat, respectively. All results for PCDD/Fs, PCDD/Fs and dl-PCBs, and ind-PCBs are below the values of 2.5 pg WHO-TEQ(2005)g(-1) fat, 5.0 pg WHO-TEQ(2005)g(-1) fat and 40 ng g(-1) fat imposed in Turkish Regulation for eggs and egg products, respectively. In all samples 2,3,4,7,8-PeCDF, 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD and PCB126 are the most prominent congeners. Mean estimated daily exposure to PCDD/Fs and dl-PCBs for Turkish population from egg is 0.011 pg WHO-TEQ(2005)d(-1)kg body weight (bw)(-1). Although the exposure levels are below the TDI of 2 pg WHO-TEQ(1998)kg bw(-1), the results were based only on consumption of egg. In order to estimate total dietary intake for Turkish population, various food items should be investigated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution.

    Science.gov (United States)

    Nishi, Akinori; Matamales, Miriam; Musante, Veronica; Valjent, Emmanuel; Kuroiwa, Mahomi; Kitahara, Yosuke; Rebholz, Heike; Greengard, Paul; Girault, Jean-Antoine; Nairn, Angus C

    2017-01-27

    The interaction of glutamate and dopamine in the striatum is heavily dependent on signaling pathways that converge on the regulatory protein DARPP-32. The efficacy of dopamine/D1 receptor/PKA signaling is regulated by DARPP-32 phosphorylated at Thr-34 (the PKA site), a process that inhibits protein phosphatase 1 (PP1) and potentiates PKA action. Activation of dopamine/D1 receptor/PKA signaling also leads to dephosphorylation of DARPP-32 at Ser-97 (the CK2 site), leading to localization of phospho-Thr-34 DARPP-32 in the nucleus where it also inhibits PP1. In this study the role of glutamate in the regulation of DARPP-32 phosphorylation at four major sites was further investigated. Experiments using striatal slices revealed that glutamate decreased the phosphorylation states of DARPP-32 at Ser-97 as well as Thr-34, Thr-75, and Ser-130 by activating NMDA or AMPA receptors in both direct and indirect pathway striatal neurons. The effect of glutamate in decreasing Ser-97 phosphorylation was mediated by activation of PP2A. In vitro phosphatase assays indicated that the PP2A/PR72 heterotrimer complex was likely responsible for glutamate/Ca 2+ -regulated dephosphorylation of DARPP-32 at Ser-97. As a consequence of Ser-97 dephosphorylation, glutamate induced the nuclear localization in cultured striatal neurons of dephospho-Thr-34/dephospho-Ser-97 DARPP-32. It also reduced PKA-dependent DARPP-32 signaling in slices and in vivo Taken together, the results suggest that by inducing dephosphorylation of DARPP-32 at Ser-97 and altering its cytonuclear distribution, glutamate may counteract dopamine/D1 receptor/PKA signaling at multiple cellular levels. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Effect of dietary antioxidants on the promotion of hepatocarcinogenesis by PCBs

    Energy Technology Data Exchange (ETDEWEB)

    Glauert, H.; Tharappel, J.; Stemm, D.; Spear, B. [Univ. of Kentucky, Lexington, KY (United States); Lehmler, H.J.; Robertson, L. [Univ. of Iowa, Iowa City, IA (United States)

    2004-09-15

    Mixtures of halogenated biphenyls as well as many individual congeners have been reported to be promoters of carcinogenesis in various liver tumor models. However, their mechanism of action is not known. A number of mechanisms have been investigated, including direct effects on signal transduction pathways, induction of oxidative stress, effects on vitamin A metabolism, and effects on intercellular communication. One mechanism by which PCBs may promote hepatic tumors is by inducing oxidative damage in the liver. Forms of oxidative damage that may be important are the induction of lipid peroxidation, the induction of oxidative DNA damage, and the alteration of gene expression. One possible mechanism for inhibiting the promoting activity of PCBs may be to increase the concentration of antioxidants in the diet. In this study, we examined if dietary selenium or antioxidant phytochemicals could inhibit the hepatic promoting activity of PCBs in rats.

  11. Behavioural effects of chemogenetic dopamine neuron activation

    NARCIS (Netherlands)

    Boekhoudt, L

    2016-01-01

    Various psychiatric disorders, including schizophrenia, attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder, have been associated with altered dopamine signalling in the brain. However, it remains unclear which specific changes in dopamine activity are related to specific

  12. Ethanol Exposure History and Alcoholic Reward Differentially Alter Dopamine Release in the Nucleus Accumbens to a Reward-Predictive Cue.

    Science.gov (United States)

    Fiorenza, Amanda M; Shnitko, Tatiana A; Sullivan, Kaitlin M; Vemuru, Sudheer R; Gomez-A, Alexander; Esaki, Julie Y; Boettiger, Charlotte A; Da Cunha, Claudio; Robinson, Donita L

    2018-06-01

    Conditioned stimuli (CS) that predict reward delivery acquire the ability to induce phasic dopamine release in the nucleus accumbens (NAc). This dopamine release may facilitate conditioned approach behavior, which often manifests as approach to the site of reward delivery (called "goal-tracking") or to the CS itself (called "sign-tracking"). Previous research has linked sign-tracking in particular to impulsivity and drug self-administration, and addictive drugs may promote the expression of sign-tracking. Ethanol (EtOH) acutely promotes phasic release of dopamine in the accumbens, but it is unknown whether an alcoholic reward alters dopamine release to a CS. We hypothesized that Pavlovian conditioning with an alcoholic reward would increase dopamine release triggered by the CS and subsequent sign-tracking behavior. Moreover, we predicted that chronic intermittent EtOH (CIE) exposure would promote sign-tracking while acute administration of naltrexone (NTX) would reduce it. Rats received 14 doses of EtOH (3 to 5 g/kg, intragastric) or water followed by 6 days of Pavlovian conditioning training. Rewards were a chocolate solution with or without 10% (w/v) alcohol. We used fast-scan cyclic voltammetry to measure phasic dopamine release in the NAc core in response to the CS and the rewards. We also determined the effect of NTX (1 mg/kg, subcutaneous) on conditioned approach. Both CIE and alcoholic reward, individually but not together, associated with greater dopamine to the CS than control conditions. However, this increase in dopamine release was not linked to greater sign-tracking, as both CIE and alcoholic reward shifted conditioned approach from sign-tracking behavior to goal-tracking behavior. However, they both also increased sensitivity to NTX, which reduced goal-tracking behavior. While a history of EtOH exposure or alcoholic reward enhanced dopamine release to a CS, they did not promote sign-tracking under the current conditions. These findings are

  13. Mesolimbic dopamine function is not altered during continuous chronic treatment of rats with typical or atypical neuroleptic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Rupniak, N M.J.; Hall, M D; Kelly, E; Fleminger, S; Kilpatrick, G; Jenner, P; Marsden, C D

    1985-01-01

    Rats were treated continuously for up to 20 months with either haloperidol (1.4-1.6 mg/kg/day), sulpiride (102-109 mg/kg/day) or clozapine (24-27 mg/kg/day). Bsub(max) for specific mesolimbic binding of TH-spiperone, TH-N, n-propylnorapomorphine or TH-piflutixol did not differ in tissue taken from animals treated for up to 12 months with haloperidol, sulpiride or clozapine by comparison to age-matched control rats. Mesolimbic dopamine (50 M)-stimulated adenylate cyclase activity was not altered in any drug treatment group. Spontaneous locomotor activity was transiently decreased during treatment with haloperidol for 1 or 3 months, but not by chronic sulpiride or clozapine treatment. Locomotor activity was not consistently increased in any drug treatment group. After 20 months of continuous drug treatment, focal bilateral application of dopamine (12.5 or 25 g) into the nucleus accumbens caused equivalent increases in locomotor activity in control rats and in animals receiving haloperidol, sulpiride of clozapine. These findings suggest that dopamine receptor blockade is not maintained in the mesolimbic area following chronic treatment with haloperidol, sulpiride or clozapine, and indicate that, under these conditions, clozapine and sulpiride may not act selectively on mesolimbic dopamine receptors. (Author).

  14. Mesolimbic dopamine function is not altered during continuous chronic treatment of rats with typical or atypical neuroleptic drugs

    International Nuclear Information System (INIS)

    Rupniak, N.M.J.; Hall, M.D.; Kelly, E.; Fleminger, S.; Kilpatrick, G.; Jenner, P.; Marsden, C.D.

    1985-01-01

    Rats were treated continuously for up to 20 months with either haloperidol (1.4-1.6 mg/kg/day), sulpiride (102-109 mg/kg/day) or clozapine (24-27 mg/kg/day). Bsub(max) for specific mesolimbic binding of 3 H-spiperone, 3 H-N, n-propylnorapomorphine or 3 H-piflutixol did not differ in tissue taken from animals treated for up to 12 months with haloperidol, sulpiride or clozapine by comparison to age-matched control rats. Mesolimbic dopamine (50 μM)-stimulated adenylate cyclase activity was not altered in any drug treatment group. Spontaneous locomotor activity was transiently decreased during treatment with haloperidol for 1 or 3 months, but not by chronic sulpiride or clozapine treatment. Locomotor activity was not consistently increased in any drug treatment group. After 20 months of continuous drug treatment, focal bilateral application of dopamine (12.5 or 25 μg) into the nucleus accumbens caused equivalent increases in locomotor activity in control rats and in animals receiving haloperidol, sulpiride of clozapine. These findings suggest that dopamine receptor blockade is not maintained in the mesolimbic area following chronic treatment with haloperidol, sulpiride or clozapine, and indicate that, under these conditions, clozapine and sulpiride may not act selectively on mesolimbic dopamine receptors. (Author)

  15. Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats.

    Science.gov (United States)

    Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D; Kennedy, Robert T; Ferrario, Carrie R

    2016-03-01

    Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk-foods" in obesity-prone and obesity-resistant rats. Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. © 2016 The Obesity Society.

  16. Ultratrace analysis of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) in human serum and cerebrospinal fluid (CSF) samples

    Energy Technology Data Exchange (ETDEWEB)

    Takasuga, T.; Senthilkumar, K.; Watanabe, K.; Takemori, H. [Shimadzu Techno Research, Inc., Kyoto (Japan); Shoda, T. [Ehime Univ. Medical Research Center, Matsuyama (Japan); Kuroda, Y. [Tokyo Metropolitan Inst. for Neuroscience, Tokyo (Japan)

    2004-09-15

    In the present study, we established pretreatment and high sensitivity analytical method of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) in serum and cerebrospinal fluid (CSF) of humans for the first time. Analyzing serum and CSF samples from humans found unique because PCBs behavior and metabolism could be discerned. Furthermore, so far studies reported concentrations of OH-PCBs in wildlife samples obtained by HRGC-LRMS or GC-ECD data. In this study, we established cleanup and analytical methods by high resolution gas chromatography-high resolution mass spectrometry (HRGC-HRMS) using 1 mL of sample. Mainly, total PCBs and OH-PCBs in the CSF were extracted by specialized developed method. Using this method, PCBs and OH-PCBs could be determined swiftly. Based on this method, major OH-PCB congeners were detected from human, serum, CSF, control serum and Rhesus monkey plasma. Present methodology developed based on the isotope dilution technique using OH-PCBs standard and thus we suggest the present methodology could apply for ultra trace analysis of OHPCBs as well as total PCBs in human samples.

  17. Ih current is necessary to maintain normal dopamine fluctuations and sleep consolidation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Alicia Gonzalo-Gomez

    Full Text Available HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep:activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest:activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels.

  18. PCBs and OH-PCBs in polar bear mother-cub pairs: a comparative study based on plasma levels in 1998 and 2008.

    Science.gov (United States)

    Bytingsvik, Jenny; Lie, Elisabeth; Aars, Jon; Derocher, Andrew E; Wiig, Øystein; Jenssen, Bjørn M

    2012-02-15

    The aim of this study was to examine the plasma concentrations and prevalence of polychlorinated biphenyls (PCBs) and hydroxylated PCB-metabolites (OH-PCBs) in polar bear (Ursus maritimus) mothers (n=26) and their 4 months old cubs-of-the-year (n=38) from Svalbard to gain insight into the mother-cub transfer, biotransformation and to evaluate the health risk associated with the exposure to these contaminants. As samplings were performed in 1997/1998 and 2008, we further investigated the differences in levels and pattern of PCBs between the two sampling years. The plasma concentrations of Σ(21)PCBs (1997/1998: 5710 ± 3090 ng/g lipid weight [lw], 2008: 2560 ± 1500 ng/g lw) and Σ(6)OH-PCBs (1997/1998: 228 ± 60 ng/g wet weight [ww], 2008: 80 ± 38 ng/g ww) in mothers were significantly lower in 2008 compared to in 1997/1998. In cubs, the plasma concentrations of Σ(21)PCBs (1997/1998: 14680 ± 5350 ng/g lw, 2008: 6070 ± 2590 ng/g lw) and Σ(6)OH-PCBs (1997/1998: 98 ± 23 ng/g ww, 2008: 49 ± 21 ng/g ww) were also significantly lower in 2008 than in 1997/1998. Σ(21)PCBs in cubs was 2.7 ± 0.7 times higher than in their mothers. This is due to a significant maternal transfer of these contaminants. In contrast, Σ(6)OH-PCBs in cubs were approximately 0.53 ± 0.16 times the concentration in their mothers. This indicates a lower maternal transfer of OH-PCBs compared to PCBs. The majority of the metabolite/precursor-ratios were lower in cubs compared to mothers. This may indicate that cubs have a lower endogenous capacity to biotransform PCBs to OH-PCBs than polar bear mothers. Exposure to PCBs and OH-PCBs is a potential health risk for polar bears, and the levels of PCBs and OH-PCBs in cubs from 2008 were still above levels associated with health effects in humans and wildlife. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Dioxins, dioxin-like PCBs and non-dioxin-like PCBs in foodstuffs : occurrence and dietary intake in the Netherlands

    NARCIS (Netherlands)

    Baars, A.J.; Bakker, M.I.; Baumann, R.A.; Boon, P.E.; Freijer, J.I.; Hoogenboom, L.A.P.; Klaveren, van J.D.; Liem, A.K.D.; Traag, W.A.; Vries, de J.

    2004-01-01

    Data on occurrence of dioxins (polychlorinated dibenzo-p-dioxins [PCDDs] and dibenzofurans [PCDFs]), dioxin-like PCBs (polychlorinated non-ortho and mono-ortho biphenyls) and non-dioxin-like PCBs (as represented by the so-called indicator-PCBs: congeners 28, 52, 101, 118, 138, 153 and 180) in food

  20. Accumulation of polychlorinated biphenyls (PCBs) and evaluation of hematological and immunological effects of PCB exposure on turtles.

    Science.gov (United States)

    Yu, Shuangying; Halbrook, Richard S; Sparling, Donald W

    2012-06-01

    Concentrations of total polychlorinated biphenyls (PCBs), Aroclor 1260, and 26 congeners were measured in liver, fat, and eggs of red-eared slider turtles (Trachemys scripta elegans) collected from ponds near or on the Paducah Gaseous Diffusion Plant (PGDP), Kentucky, USA. Concentrations of total PCBs (wet mass) ranged from 0.002 to 0.480 mg/kg, 0.028 to 0.839 mg/kg, and 0.001 to 0.011 mg/kg in liver, fat, and eggs, respectively. Concentrations of Arochlor 1260 did not exceed 0.430, 0.419, and 0.007 mg/kg in liver, fat, and eggs, respectively. Exposure to PCBs in red-eared sliders collected from the PGDP is characterized by low concentrations of moderately chlorinated mono-ortho and di-ortho congeners (PCB 153, 180, and 118). Although PCB concentrations measured in the current study were low, chronic exposure to PCBs may have altered hematology and immunity of the turtles examined. Total white blood cell count and number of heterophils were negatively correlated with concentrations of total PCBs and Arochlor 1260, respectively. However, disease and other contaminants in the study area may influence the results. Because little is known regarding the influence of PCBs on hematology and immune function in turtles, additional study is needed to better evaluate results observed in the current study.

  1. Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain.

    Science.gov (United States)

    Shnitko, Tatiana A; Taylor, Sarah C; Stringfield, Sierra J; Zandy, Shannon L; Cofresí, Roberto U; Doherty, James M; Lynch, William B; Boettiger, Charlotte A; Gonzales, Rueben A; Robinson, Donita L

    2016-06-01

    Dopamine plays a critical role in striatal and cortical function, and depletion of the dopamine precursors phenylalanine and tyrosine is used in humans to temporarily reduce dopamine and probe the role of dopamine in behavior. This method has been shown to alter addiction-related behaviors and cognitive functioning presumably by reducing dopamine transmission, but it is unclear what specific aspects of dopamine transmission are altered. We performed this study to confirm that administration of an amino acid mixture omitting phenylalanine and tyrosine (Phe/Tyr[-]) reduces tyrosine tissue content in the prefrontal cortex (PFC) and nucleus accumbens (NAc), and to test the hypothesis that Phe/Tyr[-] administration reduces phasic dopamine release in the NAc. Rats were injected with a Phe/Tyr[-] amino acid mixture, a control amino acid mixture, or saline. High-performance liquid chromatography was used to determine the concentration of tyrosine, dopamine, or norepinephrine in tissue punches from the PFC and ventral striatum. In a separate group of rats, phasic dopamine release was measured with fast-scan cyclic voltammetry in the NAc core after injection with either the Phe/Tyr[-] mixture or the control amino acid solution. Phe/Tyr[-] reduced tyrosine content in the PFC and NAc, but dopamine and norepinephrine tissue content were not reduced. Moreover, Phe/Tyr[-] decreased the frequency of dopamine transients, but not their amplitude, in freely moving rats. These results indicate that depletion of tyrosine via Phe/Tyr[-] decreases phasic dopamine transmission, providing insight into the mechanism by which this method modifies dopamine-dependent behaviors in human imaging studies.

  2. Exposure to coplanar PCBs induces endothelial cell inflammation through epigenetic regulation of NF-κB subunit p65

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Dandan; Perkins, Jordan T. [Superfund Research Center, University of Kentucky, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40536 (United States); Petriello, Michael C. [Superfund Research Center, University of Kentucky, Lexington, KY 40536 (United States); Graduate Center for Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Hennig, Bernhard, E-mail: bhennig@uky.edu [Superfund Research Center, University of Kentucky, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40536 (United States)

    2015-12-15

    Epigenetic modifications of DNA and histones alter cellular phenotypes without changing genetic codes. Alterations of epigenetic marks can be induced by exposure to environmental pollutants and may contribute to associated disease risks. Here we test the hypothesis that endothelial cell dysfunction induced by exposure to polychlorinated biphenyls (PCBs) is mediated in part though histone modifications. In this study, human vascular endothelial cells were exposed to physiologically relevant concentrations of several PCBs congeners (e.g., PCBs 77, 118, 126 and 153) followed by quantification of inflammatory gene expression and changes of histone methylation. Only exposure to coplanar PCBs 77 and 126 induced the expression of histone H3K9 trimethyl demethylase jumonji domain-containing protein 2B (JMJD2B) and nuclear factor-kappa B (NF-κB) subunit p65, activated NF-κB signaling as evidenced by nuclear translocation of p65, and up-regulated p65 target inflammatory genes, such as interleukin (IL)-6, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL-1α/β. The increased accumulation of JMJD2B in the p65 promoter led to a depletion of H3K9me3 repression mark, which accounts for the observed up-regulation of p65 and associated inflammatory genes. JMJD2B gene knockdown confirmed a critical role for this histone demethylase in mediating PCB-induced inflammation of the vascular endothelium. Finally, it was determined, via chemical inhibition, that PCB-induced up-regulation of JMJD2B was estrogen receptor-alpha (ER-α) dependent. These data suggest that coplanar PCBs may exert endothelial cell toxicity through changes in histone modifications. - Highlights: • Coplanar PCBs significantly induced histone demethylase JMJD2B expression. • Coplanar PCBs activated NF-κB through p65 up-regulation and nuclear translocation. • Histone H3K4 and K9 modifications were mediated by ER-α/JMJD2B/MLL2 complex.

  3. Evidence for distinct sodium-, dopamine-, and cocaine-dependent conformational changes in transmembrane segments 7 and 8 of the dopamine transporter

    DEFF Research Database (Denmark)

    Norregaard, Lene; Loland, Claus Juul; Gether, Ulrik

    2003-01-01

    . Inhibitors such as cocaine did not alter the effect of MTSET in M371C. The protection of M371C inactivation by dopamine required Na+. Because dopamine binding is believed to be Na+-independent, this suggests that dopamine induces a transport-associated conformational change that decreases the reactivity of M......371C with MTSET. In contrast to M371C, cocaine decreased the reaction rate of A399C with MTSET, whereas dopamine had no effect. The protection by cocaine can either reflect that Ala-399 lines the cocaine binding crevice or that cocaine induces a conformational change that decreases the reactivity of A...

  4. Dopamine and anorexia nervosa.

    Science.gov (United States)

    Södersten, P; Bergh, C; Leon, M; Zandian, M

    2016-01-01

    We have suggested that reduced food intake increases the risk for anorexia nervosa by engaging mesolimbic dopamine neurons, thereby initially rewarding dieting. Recent fMRI studies have confirmed that dopamine neurons are activated in anorexia nervosa, but it is not clear whether this response is due to the disorder or to its resulting nutritional deficit. When the body senses the shortage of nutrients, it rapidly shifts behavior toward foraging for food as a normal physiological response and the mesolimbic dopamine neurons may be involved in that process. On the other hand, the altered dopamine status of anorexics has been suggested to result from a brain abnormality that underlies their complex emotional disorder. We suggest that the outcomes of the treatments that emerge from that perspective remain poor because they target the mental symptoms that are actually the consequences of the food deprivation that accompanies anorexia. On the other hand, a method that normalizes the disordered eating behavior of anorexics results in much better physiological, behavioral, and emotional outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

    Science.gov (United States)

    Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

    2013-01-01

    Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  6. Potential new bioremediation technique of PCBs

    International Nuclear Information System (INIS)

    Bowlds, L.S.

    1992-01-01

    University of Michigan environmental engineers may have found a way to destroy toxic PCBs in contaminated riverbed sediments using sequential treatments with anaerobic and aerobic bacteria. According to the researchers, the process is the first to breakdown successfully PCBs in contaminated sediments. First anaerobic organisms remove chlorine atoms from PCBs, making them less toxic. Then aerobic bacteria chemically convert PCBs to carbon dioxide and water. The trick is putting oxygen into the system to create the switch from anaerobic to aerobic degradation. To date concentrations have been reduced from 300 mg/L to about 50 mg/L and work continues to attempt to perfect the process. EPA has been requested to test the sequential anaerobic-aerobic process on PBC-contaminated Superfund sites near Sheboygan, WI

  7. Analytical method of polychlorinated biphenyls(PCBs) in transformer oil

    Energy Technology Data Exchange (ETDEWEB)

    Shin, S.K. [National Institute of Environmental Research, Incheon (Korea); Kim, H.J.; Chung, D.; Kim, K.S.; Kim, J.K.; Chung, Y.H.; Chung, I.R.

    2004-09-15

    Polychlorinated biphenyls (PCBs) is a chlorinated biphenyl compound with the general formula C{sub 12}H{sub 10-n}/Cl{sub n}. PCBs generally occur as mixtures, where n can vary from 1 to 10. The 10 sites available for possible chlorine substitution result in 209 possible PCB congeners. There is now considerable concern regarding; the presence of PCB congeners in insulating oils used within large-scale electrical supply systems. Due to its outstanding chemical and thermal stabilities and electrical insulation properties, the commercial and industrial products of polychlorinated biphenyls (PCBs), such as Aroclors, Kaneclors, Clophens, Phenaclors etc., had been widely used as thermal oil and transformer oil from 1930s until the 1970s. PCBs from a group of persistent organic pollutants of the environment, especially dangerous to living organisms due to high toxicity, persistency, and bio-concentration in adipose tissue. Despite of this fact, PCB-contaminated oils are still commonly encountered partly because PCBs used as dielectric liquids in transformer and condenser. The source of PCBs in environments can range from used transformer oils or dielectric liquids to liquid wastes, and some PCBs contamination is occurred due to the re-use of incompletely reconditioned oil. The current action plan of Republic of Korea dictates that organizations with electrical equipment contaminated with more than 2 mg/L PCBs will need to treat as PCBs-containing wastes, and 50mg/L of PCBs or PCBs equivalent to be treated as a pure PCB preparation. In this study, transformer oils analyzed based on guideline for PCBs analytical method of transformer oil in Korea.

  8. Los PCBs salen de paseo

    Directory of Open Access Journals (Sweden)

    M. Castillo Rodríguez

    2002-12-01

    Full Text Available La exposición humana a compuestos organoclorados bioacumulables es un problema de interés sanitario no sólo por el conocimiento de la presencia en tejidos del residuo de contaminantes históricos como DDT y otros pesticidas, sino por el riesgo de exposición actual a compuestos aún en uso como el lindano, el endosulfán y los bifenilos policlorados (PCBs, entre otros. Destaca el caso particular de los PCBs, sustancias cuya producción fue prohibida debido a su peligrosidad, persistencia y toxicidad ambiental. A pesar de esta prohibición siguen funcionando una gran cantidad de aparatos que contienen volúmenes considerables de PCBs. Estos aparatos llegarán en los próximos años, si no lo han hecho ya, a la fase de residuos, por lo que es necesario asegurar su correcta eliminación para evitar su liberación al medio ambiente. El Plan Nacional para la descontaminación y eliminación de policlorobifenilos (PCBs, policloroterfenilos (PCTs y aparatos que los contengan, puesto en marcha en España en el año 2001, debe llevarse a cabo teniendo en cuenta los posibles efectos que los PCBs pueden provocar en el medio ambiente y en la salud humana y con el conocimiento de los responsables en salud pública.

  9. Dopamine

    International Nuclear Information System (INIS)

    Walters, L.

    1983-01-01

    Dopamine is an important neurotransmittor in the central nervous system. The physiological function of the peripheral dopamine receptors is unknown, but they are of therapeutic importance as dopamine is used to improve renal blood flow in shocked patients. There are 4 dopamine receptors. The classification of these dopamine receptors has been made possible by research with radiopharmaceuticals. Dopamine sensitive adenylate cyclase is an inherent part of the dopamine-1-receptor. Dopamine-1-receptors are stimulated by micromolar (physiological) concentrations of dopamine and inhibited by micromolar (supratherapeutic) concentrations of the antipsychotic drugs. The vascular effect of dopamine is mediated through the dopamine-1-receptors. Dopamine-2-receptors are responsible for the effect of dopamine at the mesolimbic, nigrostriatal and chemoreceptortrigger areas. It is activated by micromolar concentrations of dopamine and blocked by nanomolar (therapeutic) concentrations of the anti-psychotic drugs. Dopamine-3-receptors are activated by nanomolar concentrations of dopamine and inhibited by micromolar concentrations of the antipsychotic drugs. They occur on presynaptic nerve terminals and have a negative feedback effect on the liberation of dopamine, noradrenaline and serotonin. The dopamine-4-receptors are activated by nanomolar concentrations of dopamine. These are the only dopamine receptors that could be responsible for effects in the hypophysis as only nanomolar concentrations of dopamine occur there. These receptors are blocked by nanomolar concentrations of the antipsychotic drugs

  10. Elevated dopamine alters consummatory pattern generation and increases behavioral variability during learning

    Directory of Open Access Journals (Sweden)

    Mark A. Rossi

    2015-05-01

    Full Text Available The role of dopamine in controlling behavior remains poorly understood. In this study we examined licking behavior in an established hyperdopaminergic mouse model—dopamine transporter knockout (DAT KO mice. DAT KO mice showed higher rates of licking, which is due to increased perseveration of licking in a bout. By contrast, they showed increased individual lick durations, and reduced inter-lick-intervals. During extinction, both KO and control mice transiently increased variability in lick pattern generation while reducing licking rate, yet they showed very different behavioral patterns. Control mice gradually increased lick duration as well as variability. By contrast, DAT KO mice exhibited more immediate (within 10 licks adjustments—an immediate increase in lick duration variability, as well as more rapid extinction. These results suggest that the level of dopamine can modulate the persistence and pattern generation of a highly stereotyped consummatory behavior like licking, as well as new learning in response to changes in environmental feedback. Increased dopamine in DAT KO mice not only increased perseveration of bouts and individual lick duration, but also increased the behavioral variability in response to the extinction contingency and the rate of extinction.

  11. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism

    Science.gov (United States)

    The common parasite Toxoplasma gondii induces behavioral alterations in its hosts including phenotypes increasing the likelihood of its transmission in rodents and reports of psychobehavioral alterations in humans. We have found that elevated levels of dopamine are associated with the encysted stage...

  12. Role of inhalation in exposure to polychlorinated biphenyls (PCBs)

    International Nuclear Information System (INIS)

    Monarca, S.; Dominici, L.; Fatigoni, C.

    2007-01-01

    Polychlorinated biphenyls (PCBs) are a group of aromatic compounds consisting of a biphenyl variously chlorinated. Industrial production of PCBs started in 1929 and stopped in the second half of the '70s in USA and in the late 80's and 90's in Europe. PCBs are ubiquitous pollutants. The way of human exposure to PCBs is a matter of discussion. Scientific data show that the greater exposure occurs through diet. However, other available data suggest a not marginal role of the inhalation exposure. The sources of PCBs to which population are exposed depend on the amount of redistribution of these compounds released in the environment. The aim of this work is to highlight numerous studies proving that the intake of PCBs by inhalation cannot be neglected, in particular in heavily industrialized areas and where the concentration of PCBs in the environmental matrices is particularly high

  13. PCBs levels and indicator congeners in children's and adolescents' hair

    International Nuclear Information System (INIS)

    Liang, Baocui; Liu, Xinhui; Hou, Jing; Liang, Gang; Gong, Wenwen; Xu, Diandou; Zhang, Li

    2014-01-01

    Thirty polychlorinated biphenyl (PCB) congeners were determined in the hair samples collected from children (4–12) and adolescents (13–18) of Changchun city, Northeastern China. The mean concentrations of total PCBs and dioxin-like PCBs (dl-PCBs) in the adolescents' hair samples were 161.0 ng g −1 and 61.7 ng g −1 , which were relatively higher than 43.7 ng g −1 and 14.6 ng g −1 in the children's ones. Considering gender difference, the mean concentrations in the girls' hair samples were approximately two times higher than those in the boys' ones for most PCB congeners. The pentachlorinated biphenyl was the dominant homologue. It was found that the levels of total PCBs and dl-PCBs were highly correlated with PCB 118 level in the children's hair samples, and with PCB 114 level in the adolescents' ones. The result demonstrated that the two PCB congeners could be applied as the indicators to evaluate the concentrations of total PCBs and dl-PCBs in children's and adolescents' hair, respectively. -- Highlights: • PCBs levels for most congeners were higher in the adolescents' hair samples. • The mean PCBs were approximately 2 times higher for girls except few congeners. • Pentachlorinated biphenyl was the dominant homologue in the both hair samples. • PCB 118 and PCB 114 were the indicators for total PCBs and total dl-PCBs. -- The PCBs levels can be predicted conveniently by the congener-specific analysis

  14. Fetal exposure markers of dioxins and dioxin-like PCBs.

    Science.gov (United States)

    Lampa, Erik; Eguchi, Akifumi; Todaka, Emiko; Mori, Chisato

    2018-04-01

    Fetal exposure to polychlorinated biphenyls (PCBs), polychlorinated-p-dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) have been associated with a number of adverse health outcomes. Although the placenta acts as a barrier between the mother and the fetus, these contaminants transfer through the placenta exposing the fetus. Several studies have investigated placental transfer, but few have assessed the co-variation among these contaminants. Maternal blood, cord blood, and cord tissue were collected from 41 Japanese mother-infant pairs and analyzed for dioxin-like PCBs and PCDD/Fs. Hierarchical cluster analysis followed by principal component analysis were used to assess the co-variation. Two stable clusters of dioxin-like PCBs were found in maternal and cord blood. One cluster of low/medium chlorinated dioxin-like PCBs was present in all three matrices with 2,3',4,4',5-PeCB(#118) and 3,3',4,4',5-PeCB(#126) explaining the majority of the clusters' variances. Medium/high chlorinated dioxin-like PCBs clustered in maternal blood and cord blood but not in cord tissue. 2,3,4,4',5-PeCB(#114) and 2,3,3',4,4',5,5'-HpCB(#189) explained the majority of the clusters' variances. There was a substantial correlation between the sum of dioxin-like PCBs and total PCDD/F in all three matrices. The sum of the four suggested PCBs plus 3,3',4,4'-TeCB(#77) correlated well with total PCDD/F in all three matrices. Apart from the dioxin-like PCBs, little co-variation existed among the studied contaminants. The five PCBs can be used as fetal exposure markers for dioxin and dioxin-like PCBs in maternal and cord blood respectively. In cord tissue, more higher chlorinated dioxin-like PCBs need to be measured as well.

  15. Biological data on PCBs in animals other than man

    Science.gov (United States)

    Stickel, L.F.

    1972-01-01

    SUMMARY: Polychlorinated biphenyls have become ubiquitous in the world ecosystem in quantities similar to those of DDE. Experimental studies have shown that PCBs have a toxicity to mallards, pheasants, bobwhite quail, coturnix quail, red-winged blackbirds, starlings, cowbirds, and grackles that is of the same order as the toxicity of DDE to these species. Overt signs of poisoning also are similar to those caused by compounds of the DDT group. Toxic effects of DDE and Aroclor 1254 to coturnix chicks were additive, but not synergistic. PCBs containing higher percentages of chlorine are more toxic to birds than those containing lower percentages. PCBs of foreign manufacture contained contaminants to an extent that greatly increased their toxicity. Residues of PCBs in the brains of birds killed by these compounds measure in the hundreds of parts per million. PCBs may have contributed to mortality of some birds in the field. Toxicity to insects of PCBs of different degrees of chlorination is the reverse of the pattern in birds: the lower chlorinations are more toxic to insects. PCBs enhanced the toxicity of dieldrin and DDT to insects. Shrimp are very sensitive to PCBs and most will die as a result of 20-day exposure to a concentration of 5 ppb. PCBs also inhibit shell growth of oysters. Crabs are less sensitive; all accumulate residues to many times the concentrations in the water, and a test with crabs showed that they lost the residues very slowly. Growth of certain species of marine diatoms was experimentally inhibited by PCBs, but algae were not affected. The small marine crustacean, Gammarus, is sensitive to PCBs in concentrations of thousandths to tenths of a part per billion. Exposure to 5 ppb of Aroclor 1254 caused mortality of two species of fish in 14-45 days. Onset of death was delayed and was accompanied by fungus-like lesions. Rainbow trout were quickly killed by terphenyls at 10 ppb under normal oxygen conditions and at 2 ppb with reduced oxygen

  16. Guidance on the management of polychlorinated biphenyls (PCBs)

    Energy Technology Data Exchange (ETDEWEB)

    1993-11-01

    Polychlorinated biphenyls (PCBs) are a class of synthetic organic chemicals including 209 known isomers, each with from 1 to 10 chlorine atoms on a biphenyl ring. PCBs have a number of desirable properties for industrial applications including thermal stability, flame retardance, and low vapor pressure. Because of these properties, PCBs were widely used as dielectric fluid in electrical equipment such as utility transformers and capacitors. PCBs were also extensively used in hydraulic fluid and heat transfer fluid, in gaskets, as additives in cutting oils and lubricant, and in a variety of other uses. The Toxic Substances Control Act (TSCA) banned the manufacture of PCBs after 1978 in response to emerging information about the adverse health effects of PCBs and their persistence in the environment. In addition, TSCA directed the Administrator of the Environmental Protection Agency (EPA) to prescribe methods for disposal of PCBS, require marking of PCBs with warning labels, and control their use. The TSCA regulations allow continued use of PCBs provided that the use is totally enclosed and does not pose a risk to human health or the environment. However, at the end of their useful life, all PCB materials must be disposed of according to the TSCA regulations. This guidance document uses graphics and flow charts where possible to present the TSCA regulations according to management activities such as use, storage, disposal, and spill cleanup. The document is designed to be read on an as-needed basis; that is, each chapter can stand alone or may be read in combination with others to help the reader determine the regulations relevant to his or her individual situation and needs. Every attempt has been made to include the requirements of other statutes and regulations that apply to PCB materials and provide references for the reader to consult for additional information.

  17. Socially isolated rats exhibit changes in dopamine homeostasis pertinent to schizophrenia

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Steiniger-Brach, Björn; Helboe, Lone

    2011-01-01

    Post-weaning social isolation of rats produces an array of behavioral and neurochemical changes indicative of altered dopamine function. It has therefore been suggested that post-weaning social isolation mimics some aspects of schizophrenia. Here we replicate and extent these findings to include...... dopamine levels in the nucleus accumbens, it did cause a significant reduction of basal dopamine release in the prefrontal cortex. In addition, social isolation lead to a significantly larger dopamine response to an amphetamine challenge, in both the nucleus accumbens and the prefrontal cortex compared...

  18. PCBs contamination in seafood species at the Eastern Coast of Thailand.

    NARCIS (Netherlands)

    Jaikanlaya, C.; Settachan, D.; Denison, M.; Ruchirawat, M.; van den Berg, M.

    2009-01-01

    Polychlorinated biphenyls (PCBs) are a large group of persistent organic substances spread throughout the world. The most toxic PCBs are those that are dioxin-like (dl-PCBs). Environmental studies on PCBs in Thailand are limited, especially with regards to dl-PCBs. This study is one of the first in

  19. Dopamine D(3) receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: role of hyperthermia.

    Science.gov (United States)

    Baladi, Michelle G; Newman, Amy H; Nielsen, Shannon M; Hanson, Glen R; Fleckenstein, Annette E

    2014-06-05

    Methamphetamine administration causes long-term deficits to dopaminergic systems that, in humans, are thought to be associated with motor slowing and memory impairment. Methamphetamine interacts with the dopamine transporter (DAT) and increases extracellular concentrations of dopamine that, in turn, binds to a number of dopamine receptor subtypes. Although the relative contribution of each receptor subtype to the effects of methamphetamine is not fully known, non-selective dopamine D2/D3 receptor antagonists can attenuate methamphetamine-induced changes to dopamine systems. The present study extended these findings by testing the role of the dopamine D3 receptor subtype in mediating the long-term dopaminergic, and for comparison serotonergic, deficits caused by methamphetamine. Results indicate that the dopamine D3 receptor selective antagonist, PG01037, attenuated methamphetamine-induced decreases in striatal DAT, but not hippocampal serotonin (5HT) transporter (SERT), function, as assessed 7 days after treatment. However, PG01037 also attenuated methamphetamine-induced hyperthermia. When methamphetamine-induced hyperthermia was maintained by treating rats in a warm ambient environment, PG01037 failed to attenuate the effects of methamphetamine on DAT uptake. Furthermore, PG01037 did not attenuate methamphetamine-induced decreases in dopamine and 5HT content. Taken together, the present study demonstrates that dopamine D3 receptors mediate, in part, the long-term deficits in DAT function caused by methamphetamine, and that this effect likely involves an attenuation of methamphetamine-induced hyperthermia. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Dopamine D3 receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: Role of hyperthermia

    Science.gov (United States)

    Baladi, Michelle G.; Newman, Amy H.; Nielsen, Shannon M.; Hanson, Glen R.; Fleckenstein, Annette E.

    2014-01-01

    Methamphetamine administration causes long-term deficits to dopaminergic systems that, in humans, are thought to be associated with motor slowing and memory impairment. Methamphetamine interacts with the dopamine transporter (DAT) and increases extracellular concentrations of dopamine that, in turn, binds to a number of dopamine receptor subtypes. Although the relative contribution of each receptor subtype to the effects of methamphetamine is not fully known, non-selective dopamine D2/D3 receptor antagonists can attenuate methamphetamine-induced changes to dopamine systems. The present study extended these findings by testing the role of the dopamine D3 receptor subtype in mediating the long-term dopaminergic, and for comparison serotonergic, deficits caused by methamphetamine. Results indicate that the dopamine D3 receptor selective antagonist, PG01037, attenuated methamphetamine-induced decreases in striatal DAT, but not hippocampal serotonin (5HT) transporter (SERT), function, as assessed 7 days after treatment. However, PG01037 also attenuated methamphetamine-induced hyperthermia. When methamphetamine-induced hyperthermia was maintained by treating rats in a warm ambient environment, PG01037 failed to attenuate the effects of methamphetamine on DAT uptake. Furthermore, PG01037 did not attenuate methamphetamine-induced decreases in dopamine and 5HT content. Taken together, the present study demonstrates that dopamine D3 receptors mediate, in part, the long-term deficits in DAT function caused by methamphetamine, and that this effect likely involves an attenuation of methamphetamine-induced hyperthermia. PMID:24685638

  1. Altered dopamine and serotonin metabolism in motorically asymptomatic R6/2 mice.

    Directory of Open Access Journals (Sweden)

    Fanny Mochel

    Full Text Available The pattern of cerebral dopamine (DA abnormalities in Huntington disease (HD is complex, as reflected by the variable clinical benefit of both DA antagonists and agonists in treating HD symptoms. In addition, little is known about serotonin metabolism despite the early occurrence of anxiety and depression in HD. Post-mortem enzymatic changes are likely to interfere with the in vivo profile of biogenic amines. Hence, in order to reliably characterize the regional and chronological profile of brain neurotransmitters in a HD mouse model, we used a microwave fixation system that preserves in vivo concentrations of dopaminergic and serotoninergic amines. DA was decreased in the striatum of R6/2 mice at 8 and 12 weeks of age while DA metabolites, 3-methoxytyramine and homovanillic acid, were already significantly reduced in 4-week-old motorically asymptomatic R6/2 mice. In the striatum, hippocampus and frontal cortex of 4, 8 and 12-week-old R6/2 mice, serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly decreased in association with a decreased turnover of serotonin. In addition, automated high-resolution behavioural analyses displayed stress-like behaviours such as jumping and grooming and altered spatial learning in R6/2 mice at age 4 and 6 weeks respectively. Therefore, we describe the earliest alterations of DA and serotonin metabolism in a HD murine model. Our findings likely underpin the neuropsychological symptoms at time of disease onset in HD.

  2. VMAT2 and Parkinson’s disease: harnessing the dopamine vesicle

    OpenAIRE

    Lohr, Kelly M; Miller, Gary W

    2014-01-01

    Despite a movement away from dopamine-focused Parkinson’s disease (PD) research, a recent surge of evidence now suggests that altered vesicular storage of dopamine may contribute to the demise of the nigral neurons in this disease. Human studies demonstrate that the vesicular monoamine transporter 2 (VMAT2; SLC18A2) is dysfunctional in PD brain. Moreover, studies with transgenic mice suggest that there is an untapped reserve capacity of the dopamine vesicle that could be unbridled by increasi...

  3. Could dopamine agonists aid in drug development for anorexia nervosa?

    Science.gov (United States)

    Frank, Guido K W

    2014-01-01

    Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

  4. Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

    Directory of Open Access Journals (Sweden)

    Guido eFrank

    2014-11-01

    Full Text Available Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

  5. Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

    Science.gov (United States)

    Frank, Guido K. W.

    2014-01-01

    Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways. PMID:25988121

  6. Physical behavior of PCBs in the Great Lakes

    International Nuclear Information System (INIS)

    McKay, D.; Eisenreich, S.J.; Patterson, S.; Simmons, M.S.

    1983-01-01

    This book presents a review of all aspects of the physical behavior of one contaminant (PCBs) in one aquatic environment (Great Lakes). This book not only treats this topic extensively, but also serves as a model for treatment of other contaminants in other aquatic environments. This book focuses on the physical rather than biological aspects of PCBs. This focus does not imply a lack of concern for the biosphere or for the effects or toxicology of PCBs; instead, it represents an attempt to tackle a smaller problem of manageable proportions. The environmental fate of PCBs is largely controlled by physical processes, with biodegradation of lower chlorine congeners as the outstanding exception

  7. Can epidemiological studies discern subtle neurological effects due to perinatal exposure to PCBs?

    Science.gov (United States)

    Seegal, R F

    1996-01-01

    What conclusions can be drawn concerning the potential neurological effects of perinatal exposure to either PCBs, or PCBs and other fish-borne contaminants? First, by their very nature epidemiological studies are limited in their ability to detect subtle associations--including possible links between exposure to low levels of environmental contaminants and disease. As stated by Dr. Schantz, both Rogan and the Jacobsons report small changes in motor and cognitive behavior--typically less than one-half of a standard deviation--and only in the most highly exposed children. Given these small changes in CNS function, the substantive criticisms of Paneth (including the Jacobsons' choice to employ a random, rather than matched, control sample and the related fact that fish-eating mothers differed from non-fish-eating mothers on several important characteristics) and similar "generic" concerns raised by Taubes, a critical reader must question both the validity of the findings from the Michigan study and the reasons for discrepancies in results between the Jacobson and Rogan studies. Are the differences in neurobehavioral effects reported by the Jacobsons and colleagues, and Rogan and colleagues, due to the presence of confounders, exposure to different neurotoxicants, or subtle differences in methodologies? At present it is not possible to answer these questions. Nevertheless, certain commonalities exist between the Rogan and Jacobson studies, and most recently, the study conducted by Daly and colleagues in New York. All of these studies report alterations in the Brazelton Neonatal Behavioral Assessment Scale, suggesting that exposure to environmental contaminants (including PCBs) may induce subtle, transient alterations in maturation of the human CNS. Secondly, because contaminated fish contain a large number of putative developmental neurotoxicants (e.g., methyl-mercury, p,p'-DDE, PCBs, and pesticides), I am pessimistic that additional studies of human populations

  8. Comparative bioleaching of metals from pulverized and non-pulverized PCBs of cell phone charger: advantages of non-pulverized PCBs.

    Science.gov (United States)

    Joshi, Vyenkatesh; Shah, Neha; Wakte, Prashant; Dhakephalkar, Prashant; Dhakephalkar, Anita; Khobragade, Rahul; Naphade, Bhushan; Shaikh, Sajid; Deshmukh, Arvind; Adhapure, Nitin

    2017-12-01

    Sample inhomogeneity is a severe issue in printed circuit boards especially when we are comparing the bioleaching efficiency. To avoid the ambiguous results obtained due to inhomogeneity in PCBs, 12 similar cell phone chargers (of renowned company) having same make and batch number were collected from scrap market. PCBs obtained from them were used in present studies. Out of these 12, three PCBs were used separately for chemical analysis of PCBs with prior acid digestion in aqua regia. It was found that, 10.8, 68.0, and 710.9 mg/l of Zn, Pb, and Cu were present in it, respectively. Six PCBs were used for bioleaching experiment with two variations, pulverized and non-pulverized. Though the pulverized sample have shown better leaching than non-pulverized one, former has some disadvantages if overall recycling of e-waste (metallic and nonmetallic fraction) is to be addressed. At the end of leaching experiments, copper was recovered using a simple setup of electrodeposition and 92.85% recovery was attained. The acidophiles involved in bioleaching were identified by culture dependent and culture independent techniques such as DGGE and species specific primers in PCR.

  9. alpha-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia.

    Science.gov (United States)

    Cappon, G D; Broening, H W; Pu, C; Morford, L; Vorhees, C V

    1996-10-01

    Methamphetamine (MA) administration to adult rats (4 x 10 mg/kg s.c.) induces neurotoxicity predominately characterized by a persistent reduction of neostriatal dopamine (DA) content. Hyperthermia following MA administration potentiates the resulting DA depletion. DA-derived free radicals are postulated to be a mechanism through which MA-induced neurotoxicity is produced. The spin trapping agent PBN reacts with free radicals to form nitroxyl adducts, thereby preventing damaging free radical reactions with cellular substrates. MA with saline pretreatment (Sal-MA) reduced neostriatal DA by 55% (P protection. PBN pretreatment did not alter MA-induced hyperthermia. Thus, PBN does not attenuate MA-induced neurotoxicity by reducing MA-induced hyperthermia. These results support a role for free radicals in the generation of MA-induced dopaminergic neurotoxicity.

  10. Hydroxylated PCBs in abiotic environmental matrices. Precipitation and surface waters

    Energy Technology Data Exchange (ETDEWEB)

    Darling, C.; Alaee, M.; Campbell, L.; Pacepavicius, G.; Ueno, D.; Muir, D. [National Water Research Institute, Burlington, ON (Canada)

    2004-09-15

    Hydroxylated PCBs (OH-PCBs) are of great interest environmentally because of their potential thyroidogenic effects. OH-PCBs can compete with thyroxine for binding sites on transthyretin, one of the three main thyroid hormone transport proteins in mammals1. The chemical structures of some OH-PCBs with a para OH group and adjacent chlorine atoms, particularly 4-OH-CB109, 4- OH-CB146, and 4-OH-CB187, share a similar structure to the thyroid hormones (T3 and T4), which have a para OH with adjacent iodine atoms. A number of OH-PCBs have been identified in the blood of humans and biota during the last 5 to 10 years, however, reports on the identity, presence and levels of OH-PCBs are limited. This presentation describes preliminary studies on the presence of OH-PCBs in abiotic samples and comparisons of congener patterns with biological samples. We have previously shown that OHPCBs were present in lake trout from the Great Lakes and nearby large lakes as well as in nearshore environments. We hypothesized that some of the OH-PCB present in fish might be from abiotic formation in water or the atmosphere, or from microbial oxidation of PCBs and/or deconjugation of PCB metabolites in waste treatment plants.

  11. Kappa-opioid receptor signaling in the striatum as a potential modulator of dopamine transmission in cocaine dependence

    Directory of Open Access Journals (Sweden)

    Pierre eTrifilieff

    2013-06-01

    Full Text Available Cocaine addiction is accompanied by a decrease in striatal dopamine signaling, measured as a decrease in dopamine D2 receptor binding as well as blunted dopamine release in the striatum. These alterations in dopamine transmission have clinical relevance, and have been shown to correlate with cocaine-seeking behavior and response to treatment for cocaine dependence. However, the mechanisms contributing to the hypodopaminergic state in cocaine addiction remain unknown. Here we review the Positron Emission Tomography (PET imaging studies showing alterations in D2 receptor binding potential and dopamine transmission in cocaine abusers and their significance in cocaine-seeking behavior. Based on animal and human studies, we propose that the kappa receptor/dynorphin system, because of its impact on dopamine transmission and upregulation following cocaine exposure, could contribute to the hypodopaminergic state reported in cocaine addiction, and could thus be a relevant target for treatment development.

  12. Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

    OpenAIRE

    Siciliano, Cody A.; Fordahl, Steve C.; Jones, Sara R.

    2016-01-01

    Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Her...

  13. Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

    Science.gov (United States)

    Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

    2016-05-01

    Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

  14. Developmental disorders of the brain can be caused by PCBs; low doses of hydroxy-PCBs disrupt thyroid hormone-dependent dendrite formation from Purkinje neurons in culture

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, Y; Kimura-Kuroda, J [Tokyo Metropol. Inst. for Neuroscience, Tokyo (Japan); Nagata, I [CREST/ JST, Tokyo (Japan)

    2004-09-15

    Exposure to some environmental chemicals during the perinatal period causes developmental disorders of the brain. Cognitive impairment and hyperactivity in infants were reported in Taiwan, known as Yu-cheng incidents caused by the accidental contamination of polychlorinated biphenyls (PCBs). Together with recent experimental data, Kuroda proposes a hypothesis that spatio-temporal disruptions of developing neuronal circuits by PCB exposure can cause the comobidity of learning disorders (LD), attention deficit hyperactivity disorder (ADHD) and autsm with the co-exposure to other environmental chemicals. PCBs and hydroxylated PCBs (OH-PCBs) have similar chemical structures to thyroid hormones (TH), thyroxine (T4) and triiodothyronine (T3). TH deficiency in the perinatal period causes cretinism children with severe cognitive and mental retardation. In primate model, Rice demonstrates that postnatal exposure to PCBs can dramatically influence later behavioral function. Epidemiological studies also indicate the possible developmental neurotoxicity of PCBs accumulated in human bodies. However, the precise underlying mechanisms and which types of PCB or OH-PCB with such effects have yet to be elucidated. It is important to establish a simple, reproducible, and sensitive in vitro assay for determining the effects of PCBs and OH-PCBs on the development of the central nervous system. Recently Iwasaki et al. established a reporter assay system and disclosed that low doses of PCBs potentially interfere TH-dependent gene expressions. This is the first demonstration that PCBs and OH-PCBs directly affect TH-receptor (TR)-mediated gene expressions crucial to the brain development, through unique mechanism. We also have demonstrated TH-dependent development of Purkinje neurons in vitro using a serum-free chemically defined medium. The degree of dendritic development of Purkinje cells is TH dose-dependent and exhibits high sensitivity in the pM order. Therefore, in the present study

  15. Dietary fat interacts with PCBs to induce changes in lipid metabolism in LDL receptor deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Hennig, B.; Reiterer, G.; Toborek, M.; Matveev, S.V.; Daugherty, A.; Smart, E. [Univ. of Kentucky, Lexington (United States); Robertson, L.W. [Univ. of Iowa, Iowa City (United States)

    2004-09-15

    From epidemiological studies, there is substantial evidence that cardiovascular diseases are linked to environmental pollution and that exposure to polycyclic and/or polyhalogenated aromatic hydrocarbons can lead to human cardiovascular toxicity. A major route of exposure to PCBs in humans is via oral ingestion of contaminated food products. Therefore, circulating environmental contaminants derived from diets, such as PCBs, are in intimate contact with the vascular endothelium. Endothelial activation and dysfunction is an important factor in the overall regulation of vascular lesion pathology. In addition to endothelial barrier dysfunction, another functional change in atherosclerosis is the activation of the endothelium that is manifested as an increase in the expression of specific cytokines and adhesion molecules. These cytokines and adhesion molecules are proposed to mediate the inflammatory aspects of the disease by regulating the vascular entry of leukocytes. Alterations in lipid profile and lipid metabolism as a result of exposure to PCBs may be important components of endothelial cell dysfunction. Little is known about the interaction of dietary fats and PCBs in the pathology of atherosclerosis. We have reported a significant disruption in endothelial barrier function when cells were exposed to linoleic acid. In the current study we aimed to demonstrate the PCB-fatty acid interaction in vivo and hypothesized that PCB toxicity can be modulated by the type of fat consumed.

  16. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism.

    Directory of Open Access Journals (Sweden)

    Emese Prandovszky

    Full Text Available The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasite's life cycle. The mechanism(s responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense staining of encysted parasites. Based on these analyses, T. gondii orchestrates a significant increase in dopamine metabolism in neural cells. Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also found in intracellular tissue cysts in brain tissue with antibodies specific for the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism for parasite-induced behavioral changes. The observed effects on dopamine metabolism could also be relevant in interpreting reports of psychobehavioral changes in toxoplasmosis-infected humans.

  17. PCDFs, PCDDs, non-ortho PCBs, and mono-ortho PCBs in northern fulmars from the Faroe Islands

    Energy Technology Data Exchange (ETDEWEB)

    Ericson, I.M.; Hagberg, J.; Bavel van, B.; Lindstrom, G. [Orebro Univ., Orebro (Sweden). MTM Research Centre; Dam, M. [Food and Environment Agency, Torshavn, Faroe Islands (Denmark); Jensen, J.K.; Danielsen, J. [Faroese Museum of Natural History, Faroe Islands (Denmark)

    2005-07-01

    Eggs and tissues of Northern Fulmars have been used to monitor the contamination of the Canadian Arctic marine environment since 1975. Dioxin levels for northern fulmars in the Arctic are among the highest reported for birds. This study reported the results of analyses of dioxins (PCDDs) and non- and mono-ortho polychlorinated biphenyls (PCBs) in liver tissue from juvenile northern fulmars from the Faeroe Islands in 2003. The samples were collected during a traditional hunt and ground with anhydrous sodium sulfate. Sample extraction was performed using supercritical fluid extraction coupled to a solid phase liquid chromatography trap (SFE-LC). Target compounds were collected on a solid phase trap containing AX-21 carbon on ODS silica and eluted with 6 ml n-hexane/dichloromethane for non-planar compounds and xylene for planar compounds. PCDD and planar PCB analysis was performed on an a high resolution gas chromatography (GC) mass spectrometer (MS) operating at 10,000 resolution using EI ionization at 35 eV. Concentrations of PCDFs, PCDDs, non, and mono-ortho PCBs were detected in all samples. High levels of mono-ortho PCBs were detected, as well as non-ortho PCBs, PCDFs, and PCDDs. It was concluded that levels and congener patterns in fulmars from the Faroe Islands and the Canadian Arctic were comparable. However, slightly higher levels were detected in the Faeroe Islands samples. 9 refs., 1 tab., 2 figs.

  18. Adolescent social defeat alters markers of adult dopaminergic function.

    Science.gov (United States)

    Novick, Andrew M; Forster, Gina L; Tejani-Butt, Shanaz M; Watt, Michael J

    2011-08-10

    Stressful experiences during adolescence can alter the trajectory of neural development and contribute to psychiatric disorders in adulthood. We previously demonstrated that adolescent male rats exposed to repeated social defeat stress show changes in mesocorticolimbic dopamine content both at baseline and in response to amphetamine when tested in adulthood. In the present study we examined whether markers of adult dopamine function are also compromised by adolescent experience of social defeat. Given that the dopamine transporter as well as dopamine D1 receptors act as regulators of psychostimulant action, are stress sensitive and undergo changes during adolescence, quantitative autoradiography was used to measure [(3)H]-GBR12935 binding to the dopamine transporter and [(3)H]-SCH23390 binding to dopamine D1 receptors, respectively. Our results indicate that social defeat during adolescence led to higher dopamine transporter binding in the infralimbic region of the medial prefrontal cortex and higher dopamine D1 receptor binding in the caudate putamen, while other brain regions analyzed were comparable to controls. Thus it appears that social defeat during adolescence causes specific changes to the adult dopamine system, which may contribute to behavioral alterations and increased drug seeking. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Decomposition of PCBs in oils using gamma radiolysis

    International Nuclear Information System (INIS)

    Mincher, B.J.; Arbon, R.E.; Schwendiman, G.L.

    1996-01-01

    This paper investigates the radiolysis of the polychlorinated biphenyls (PCBs) in several oil matrices. The results of mechanism and kinetic studies in isooctane are presented. The decomposition of PCBs in isooctane is shown to occur by reductive dechlorination due to electron capture and to proceed with pseudo-first-order kinetics. The rate is dependent on the initial PCB concentration. Electron capture detection gas chromatograms confirm that dechlorination also occurs with commercial Aroclor PCBs in irradiated transformer and hydraulic oils. The results of a demonstration experiment involving PCB contaminated waste hydraulic oils are presented

  20. Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts

    DEFF Research Database (Denmark)

    Cumming, P; Danielsen, E H; Vafaee, M

    2001-01-01

    , both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers...... for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However...

  1. Unilateral Lesion of Dopamine Neurons Induces Grooming Asymmetry in the Mouse.

    Science.gov (United States)

    Pelosi, Assunta; Girault, Jean-Antoine; Hervé, Denis

    2015-01-01

    Grooming behaviour is the most common innate behaviour in animals. In rodents, it consists of sequences of movements organized in four phases, executed symmetrically on both sides of the animal and creating a syntactic chain of behavioural events. The grooming syntax can be altered by stress and novelty, as well as by several mutations and brain lesions. Grooming behaviour is known to be affected by alterations of the dopamine system, including dopamine receptor modulation, dopamine alteration in genetically modified animals, and after brain lesion. While a lot is known about the initiation and syntactic modifications of this refined sequence of movements, effects of unilateral lesion of dopamine neurons are unclear particularly regarding the symmetry of syntactic chains. In the present work we studied grooming in mice unilaterally lesioned in the medial forebrain bundle by 6-hydroxydopamine. We found a reduction in completion of grooming bouts, associated with reduction in number of transitions between grooming phases. The data also revealed the development of asymmetry in grooming behaviour, with reduced tendency to groom the contralateral side to the lesion. Symmetry was recovered following treatment with L-DOPA. Thus, the present work shows that unilateral lesion of dopamine neurons reduces self-grooming behaviour by affecting duration and numbers of events. It produces premature discontinuation of grooming chains but the sequence syntax remains correct. This deficient grooming could be considered as an intrinsic symptom of Parkinson's disease in animal models and could present some similarities with abnormalities of motor movement sequencing seen in patients. Our study also suggests grooming analysis as an additional method to screen parkinsonism in animal models.

  2. Dopamine controls Parkinson's tremor by inhibiting the cerebellar thalamus.

    Science.gov (United States)

    Dirkx, Michiel F; den Ouden, Hanneke E M; Aarts, Esther; Timmer, Monique H M; Bloem, Bastiaan R; Toni, Ivan; Helmich, Rick C

    2017-03-01

    Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor. From a sample of 40 patients with Parkinson's disease, we selected 15 patients with a clearly tremor-dominant phenotype. We compared tremor-related activity and effective connectivity (using combined electromyography-functional magnetic resonance imaging) on two occasions: ON and OFF dopaminergic medication. Building on a recently developed cerebral model of Parkinson's tremor, we tested the effect of dopamine on cerebral activity associated with the onset of tremor episodes (in the basal ganglia) and with tremor amplitude (in the cerebello-thalamo-cortical circuit). Dopaminergic medication reduced clinical resting tremor scores (mean 28%, range -12 to 68%). Furthermore, dopaminergic medication reduced tremor onset-related activity in the globus pallidus and tremor amplitude-related activity in the thalamic ventral intermediate nucleus. Network analyses using dynamic causal modelling showed that dopamine directly increased self-inhibition of the ventral intermediate nucleus, rather than indirectly influencing the cerebello-thalamo-cortical circuit through the basal ganglia. Crucially, the magnitude of thalamic self-inhibition predicted the clinical dopamine response of tremor. Dopamine reduces resting tremor by potentiating inhibitory mechanisms in a cerebellar nucleus of the thalamus (ventral intermediate nucleus). This suggests that altered dopaminergic projections to the cerebello-thalamo-cortical circuit have a role

  3. Polychlorinated biphenyls (PCBs)

    Energy Technology Data Exchange (ETDEWEB)

    Brecher, R.; Smith, C.; Montemayor, B. [GlobalTox International Consultants Inc., Guelph, ON (Canada)

    2001-03-01

    A brief characterization of PCBs is provided, summarizing their toxicity, acute and chronic effects, genotoxicity, carcinogenicity and reproductive and developmental toxicity. A quick reference chart which includes a description of the class of compounds, synonyms, uses, environmental fate, sources, exposure and selected regulatory information, is also included.

  4. Accumulation features and temporal trends of PCDDs, PCDFs and PCBs in Baikal seals (Pusa sibirica)

    International Nuclear Information System (INIS)

    Imaeda, Daisuke; Kunisue, Tatsuya; Ochi, Yoko; Iwata, Hisato; Tsydenova, Oyuna; Takahashi, Shin; Amano, Masao; Petrov, Evgeny A.; Batoev, Valeriy B.; Tanabe, Shinsuke

    2009-01-01

    This study investigated the accumulation features and temporal trends of PCDD/Fs, dioxin-like PCBs (DL-PCBs) and non-dioxin-like PCBs (NDL-PCBs) in the blubber of Baikal seals collected in 1992 and 2005. DL-PCBs (480-3600 ng/g) and NDL-PCBs (980-35,000 ng/g) were dominant contaminants. Concentrations of PCDDs and PCBs in males were significantly higher than in females. In males, age-dependent accumulation was observed for PCDDs, mono-ortho PCBs and NDL-PCBs. PCDFs and non-ortho PCBs showed no such trends, implying that exposure of seals to these contaminants has been decreasing in recent years. No decreasing temporal trend was observed for PCDDs, mono-ortho PCBs and NDL-PCBs, suggesting that Baikal seals are still exposed to PCDDs and PCBs. TEQs of PCDDs and mono-ortho PCBs in seals collected in 2005 accounted for 62-77% of total TEQs. The TEQ levels in 40% of the specimens exceeded the threshold level for immunosuppression observed in harbor seals (209 pg/g). - Concentrations of PCDDs and PCBs remain high in Baikal seals

  5. PCBs contamination in seafood species at the Eastern Coast of Thailand.

    Science.gov (United States)

    Jaikanlaya, Chate; Settachan, Daam; Denison, Michael S; Ruchirawat, Mathuros; van den Berg, Martin

    2009-06-01

    Polychlorinated biphenyls (PCBs) are a large group of persistent organic substances spread throughout the world. The most toxic PCBs are those that are dioxin-like (dl-PCBs). Environmental studies on PCBs in Thailand are limited, especially with regards to dl-PCBs. This study is one of the first in this country that demonstrates contamination of seafood with PCBs and determines the levels of PCBs and total dioxin like activity in mussels, oysters and shrimp, from the Eastern Coast of Thailand. Sixty pooled samples of mussels and twenty-seven pooled samples of oysters were collected from cultivation farms and twenty-one pooled samples of shrimp were collected from fisherman piers. Qualitative and quantitative measurements of 49 PCB congeners was obtained by HRGC-ECD analysis and total dioxin-like activity using the CAFLUX bioassay. Total PCB concentrations varied between three species, ranging between 19 and 1100 ng g(-1) lipid adjusted weight, and the levels of PCBs in shrimp was three time higher than that in mussels and oysters. With respected to the pattern of PCB congeners, it implied that the source of PCBs exposure in this area could be from the regional contamination. The calculated CAFLUX bioanalytical equivalents (BEQs) values ranged between 0.8 and 18 pg BEQ g(-1) lipid adjusted weight, and showed a good relationship with the chemical-derived TEQs. Therefore, the CAFLUX bioassay can be used for effective screening of dioxin-like activity in marine species effectively.

  6. Mode of action of dioxin-like versus non-dioxin-like PCBs

    Energy Technology Data Exchange (ETDEWEB)

    Schoeters, G. [VITO (Flemish Institute for Technological Research), Dept. of Environemental Toxicology (Belgium)]|[Antwerp Univ. (Belgium); Birnbaum, L. [United States Environmental Protection Agency, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory (United States)

    2004-09-15

    Exposure of humans to polychlorinated biphenyls has been associated with different adverse effects such as immune impairment, changes in hormone levels, reproductive and neuropsychological changes and cancer. It is difficult to attribute the observed effects to either dioxin-like, non-dioxin-like PCBs or to both. All known human exposures are mixed, comprising dioxin and non-dioxin like PCB congeners as well as dioxins and furans. The purpose of this work was to evaluate, based on mechanistic data available in the open literature, whether non-dioxin like PCBs (NDL-PCBs) themselves may pose specific health risks. It is clear that dioxin and NDL-PCBs differ in the spectrum of metabolizing enzymes they induce, but the mechanistic links to health of these biochemical changes remain unclear at the moment. NDL-PCBs also cause immunotoxicity and tumor promotion via different mechanisms than do dioxin-like PCBs. We focus on neurotoxicity which has been associated with developmental exposure to PCBs and which is considered as one of the most sensitive adverse health effects.

  7. Dopamine transporters govern diurnal variation in extracellular dopamine tone

    OpenAIRE

    Ferris, Mark J.; España, Rodrigo A.; Locke, Jason L.; Konstantopoulos, Joanne K.; Rose, Jamie H.; Chen, Rong; Jones, Sara R.

    2014-01-01

    The mechanism for diurnal (i.e., light/dark) oscillations in extracellular dopamine tone in mesolimbic and nigrostriatal systems is unknown. This is because, unlike other neurotransmitter systems, variation in dopamine tone does not correlate with variation in dopamine cell firing. The current research pinpoints the dopamine transporter as a critical governor of diurnal variation in both extracellular dopamine tone and the intracellular availability of releasable dopamine. These data describe...

  8. Neuroimaging of the Dopamine/Reward System in Adolescent Drug Use

    Science.gov (United States)

    Ernst, Monique; Luciana, Monica

    2015-01-01

    Adolescence is characterized by heightened risk-taking, including substance misuse. These behavioral patterns are influenced by ontogenic changes in neurotransmitter systems, particularly the dopamine system, which is fundamentally involved in the neural coding of reward and motivated approach behavior. During adolescence, this system evidences a peak in activity. At the same time, the dopamine system is neuroplastically altered by substance abuse, impacting subsequent function. Here, we describe properties of the dopamine system that change with typical adolescent development and that are altered with substance abuse. Much of this work has been gleaned from animal models due to limitations in measuring dopamine in pediatric samples. Structural and functional neuroimaging techniques have been used to examine structures that are heavily DA-innervated; they measure morphological and functional changes with age and with drug exposure. Presenting marijuana abuse as an exemplar, we consider recent findings that support an adolescent peak in DA-driven reward-seeking behavior and related deviations in motivational systems that are associated with marijuana abuse/dependence. Clinicians are advised that (1) chronic adolescent marijuana use may lead to deficiencies in incentive motivation, (2) that this state is due to marijuana’s interactions with the developing DA system, and (3) that treatment strategies should be directed to remediating resultant deficiencies in goal-directed activity. PMID:26095977

  9. Enduring increases in anxiety-like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats.

    Science.gov (United States)

    Yorgason, Jordan T; España, Rodrigo A; Konstantopoulos, Joanne K; Weiner, Jeffrey L; Jones, Sara R

    2013-03-01

    Social isolation (SI) rearing, a model of early life stress, results in profound behavioral alterations, including increased anxiety-like behavior, impaired sensorimotor gating and increased self-administration of addictive substances. These changes are accompanied by alterations in mesolimbic dopamine function, such as increased dopamine and metabolite tissue content, increased dopamine responses to cues and psychostimulants, and increased dopamine neuron burst firing. Using voltammetric techniques, we examined the effects of SI rearing on dopamine transporter activity, vesicular release and dopamine D2-type autoreceptor activity in the nucleus accumbens core. Long-Evans rats were housed in group (GH; 4/cage) or SI (1/cage) conditions from weaning into early adulthood [postnatal day (PD) 28-77]. After this initial housing period, rats were assessed on the elevated plus-maze for an anxiety-like phenotype, and then slice voltammetry experiments were performed. To study the enduring effects of SI rearing on anxiety-like behavior and dopamine terminal function, another cohort of similarly reared rats was isolated for an additional 4 months (until PD 174) and then tested. Our findings demonstrate that SI rearing results in lasting increases in anxiety-like behavior, dopamine release and dopamine transporter activity, but not D2 activity. Interestingly, GH-reared rats that were isolated as adults did not develop the anxiety-like behavior or dopamine changes seen in SI-reared rats. Together, our data suggest that early life stress results in an anxiety-like phenotype, with lasting increases in dopamine terminal function. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  10. Dopamine regulation of [3H]acetylcholine release from guinea-pig stomach

    International Nuclear Information System (INIS)

    Kusunoki, M.; Taniyama, K.; Tanaka, C.

    1985-01-01

    The involvement of dopamine receptors in cholinergic transmission of guinea-pig stomach was investigated by analyzing the effects of dopamine receptor agonists and antagonists on acetylcholine (ACh) release from this organ. Electrical stimulation (1-20 Hz) of strips of guinea-pig stomach preloaded with [ 3 H] choline induced a [ 3 H]ACh release that was calcium dependent and tetrodotoxin sensitive. Dopamine inhibited this transmural stimulation-induced [ 3 H]ACh release in a concentration-dependent manner (10(-8)-10(-4) M). This effect of dopamine was not altered by 10(-5) M hexamethonium, thereby suggesting that the major dopamine receptors are located on the postganglionic cholinergic neurons. Concentration-response curves for dopamine on [ 3 H]ACh release were inhibited by haloperidol, sulpiride and domperidone but not by prazosin, yohimbine, propranolol and ketanserin. LY 171555, an agonist for the D2 dopamine receptor, but not SKF 38-393, an agonist for the D1 dopamine receptor, to some extent decreased the release of [ 3 H]ACh induced by transmural stimulation. In view of the results, the release of ACh from postganglionic cholinergic neurons is probably required through dopamine receptors antagonized by D2 antagonists but not by adrenergic or serotonin receptor antagonists

  11. Developmental origins of brain disorders: roles for dopamine

    Directory of Open Access Journals (Sweden)

    Kelli M Money

    2013-12-01

    Full Text Available Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders.

  12. Polychlorinated Biphenyls (PCBs) in Predator and Bottom-Feeding Fish from Abiquiu and Cochiti Reservoirs in North-Central New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    G.J. Gonzales, P.R. Fresquez

    2006-03-01

    Concern has existed for years that the Los Alamos National Laboratory (LANL), a complex of nuclear weapons research and support facilities, has released polychlorinated biphenyls (PCBs) to the environment that may have reached adjacent bodies of water through canyons that connect them. In 1997, we began measuring PCBs in fish in the Rio Grande upstream and downstream of ephemeral streams that cross LANL and later began sampling fish in Abiquiu and Cochiti reservoirs, which are situated on the Rio Chama and Rio Grande upstream and downstream of LANL, respectively. In 2005, six species of fish from Abiquiu and Cochiti reservoirs were collected and the edible portion (fillets) was analyzed for 209 possible PCB congeners. Fish from the reservoirs were last sampled in 2001. Mean total PCB concentrations in fish from Abiquiu Reservoir ({mu} = 2.4 ng/g) were statistically similar ({alpha} = 0.01; P (T{le}t) [range = 0.23-0.71]) to mean total PCB concentrations in fish from Cochiti Reservoir ({mu} = 2.7 ng/g), implying that LANL is not the source of PCBs in fish in Cochiti Reservoir. The levels of PCBs in fish from Cochiti Reservoir generally appear to be declining, at least since 2001, which is when PCB levels might have peaked resulting from storm water runoff after the Cerro Grande Fire. Although a PCB ''fingerprinting'' method can be used to relate PCB ''signatures'' in one area to signatures in another area, this method of implicating the source of PCBs cannot be effectively used for biota because they alter the PCB signature through metabolic processes. Regardless of the source of the PCBs, certain species of fish (catfish and carpsuckers) at both Abiquiu and Cochiti reservoirs continue to harbor levels of PCBs that could be harmful to human health if they are consistently eaten over a long period of time. Bottom-feeding fish (carpsucker and catfish) from Cochiti Reservoir contained statistically higher levels of total PCBs

  13. Developmental dental defects in children exposed to PCBs

    Energy Technology Data Exchange (ETDEWEB)

    Jan, J. [Ljubljana Univ. (Slovenia). Fac. of Medicine; Sovcikova, E.; Kovrizhnykh, I.; Wimmerova, S.; Trnovec, T. [Slovak Medical Univ., Bratislava (Slovakia). Inst. of Preventive and Clinical Medicine; Kocan, A. [Institute of Preventive and Clinical Medicine, Bratislava (Slovakia). Dept. of Toxic Organic Pollutants

    2004-09-15

    Developing enamel is sensitive to a wide range of local and systemic disturbances. Because of the absolute metabolic stability of its structure, changes in enamel during its development are permanent in nature. Polychlorinated biphenyls (PCB) have been shown to disturb tooth development in experimental animals, but only limited amounts of data exist on their adverse effects in humans. Dental changes such as mottled, chipped, carious, and neonatal teeth have been reported in accidentally exposed humans. Nevertheless, co-contamination with polychlorinated dibenzo-furans (PCDFs) was largely responsible for the overall toxicity4. Alaluusua et al. found that developmental dental defects were correlated with the total exposure to polychlorinated aromatic hydrocarbons via mother's milk. The correlation was strong with exposure to prevailing levels of polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) but weak with exposure to PCBs alone. In our previous study we have shown developmental dental defects in children exposed to PCBs alone6, suggesting that the developing human teeth are vulnerable to PCBs. In the Michalovce region of eastern Slovakia, PCBs from a chemical plant manufacturing Delors contaminated the surrounding district7. The total serum PCB levels in samples from the general population there exceeded by several times the background levels in subjects living in a comparable unexposed Svidnik district. PCB levels in breast milk samples in the Michalovce region were the highest in Slovakia. Levels of toxic polychlorinated aromatics (PCDFs, PCNs, and planar PCBs) in technical Delors were high. The aim of this study was to evaluate the effects of long-term exposure to PCBs, measured at the individual level, on developmental dental defects in children in eastern Slovakia.

  14. Assessment of exposure and transfer of dioxins, dioxin-like PCBs and PCBs. Literature review; Expositionsbetrachtung und Beurteilung des Transfers von Dioxinen, dioxinaehnlichen PCB und PCB. Literaturstudie

    Energy Technology Data Exchange (ETDEWEB)

    Hennecke, Dieter [Fraunhofer-Institut fuer Molekularbiologie und Angewandte Oekologie (IME), Schmallenberg (Germany); Duering, Rolf-Alexander; Becker, Leonie [Giessen Univ. (Germany). Inst. fuer Bodenkunde und Bodenerhaltung

    2011-09-15

    Causal correlations between environmental contamination with PCBs and PCDD/Fs and food and feed contamination with these substances are not been found so far. Because of the high importance of the transfer of these substances into the food chain this is subject to wide research. The present literature review summarizes the actual knowledge regarding emission, exposition and transfer of PCBs and Dioxins within the food chain. A particular focus has been laid to sources of emission, distribution processes and exposure assessment for environment and consumer. International publications as well as publications and reports on a German national level and so called ''grey'' literature were evaluated. In general it can be noticed that comparison of different publications is difficult since the authors usually do not differentiate between non-dioxin-like PCBs (ndl-PCBs) and dioxin-like PCBs (dl-PCBs). Most authors mix dl-PCBs and ndl-PCBs, a breakdown of the PCBs in single congeners is rarely given. Extended Abstract Due to atmospheric translocation PCBs and PCDD/Fs are ubiquitous distributed in the environment. The emissions in Germany could be reduced drastically in the first half of the nineties due to regulatory restrictions. At the same time contaminations detected in food and feed dropped down. But since 1997 no significant further reduction of environmental concentrations of PCBs and PCDD/Fs can be observed. Present emissions of PCBs and PCDD/Fs derive from nonpoint sources mainly, e.g. remobilisation from soils and sediments by surface erosion and volatilization. Further increasing emissions of PCDD/Fs are expected due to promotion of renewable energies (combustion of wood). A short term reduction of environmental concentrations is not likely due to the persistence of the compounds. Major exposure pathway for plants is via dry and wet deposition of contaminated particles and volatiles, depending on the physical-chemical properties of the various

  15. Assessment of exposure and transfer of dioxins, dioxin-like PCBs and PCBs. Literature review; Expositionsbetrachtung und Beurteilung des Transfers von Dioxinen, dioxinaehnlichen PCB und PCB. Literaturstudie

    Energy Technology Data Exchange (ETDEWEB)

    Hennecke, Dieter [Fraunhofer-Institut fuer Molekularbiologie und Angewandte Oekologie (IME), Schmallenberg (Germany); Duering, Rolf-Alexander; Becker, Leonie [Giessen Univ. (Germany). Inst. fuer Bodenkunde und Bodenerhaltung

    2011-09-15

    Causal correlations between environmental contamination with PCBs and PCDD/Fs and food and feed contamination with these substances are not been found so far. Because of the high importance of the transfer of these substances into the food chain this is subject to wide research. The present literature review summarizes the actual knowledge regarding emission, exposition and transfer of PCBs and Dioxins within the food chain. A particular focus has been laid to sources of emission, distribution processes and exposure assessment for environment and consumer. International publications as well as publications and reports on a German national level and so called ''grey'' literature were evaluated. In general it can be noticed that comparison of different publications is difficult since the authors usually do not differentiate between non-dioxin-like PCBs (ndl-PCBs) and dioxin-like PCBs (dl-PCBs). Most authors mix dl-PCBs and ndl-PCBs, a breakdown of the PCBs in single congeners is rarely given. Extended Abstract Due to atmospheric translocation PCBs and PCDD/Fs are ubiquitous distributed in the environment. The emissions in Germany could be reduced drastically in the first half of the nineties due to regulatory restrictions. At the same time contaminations detected in food and feed dropped down. But since 1997 no significant further reduction of environmental concentrations of PCBs and PCDD/Fs can be observed. Present emissions of PCBs and PCDD/Fs derive from nonpoint sources mainly, e.g. remobilisation from soils and sediments by surface erosion and volatilization. Further increasing emissions of PCDD/Fs are expected due to promotion of renewable energies (combustion of wood). A short term reduction of environmental concentrations is not likely due to the persistence of the compounds. Major exposure pathway for plants is via dry and wet deposition of contaminated particles and volatiles, depending on the physical-chemical properties of the various congeners. Uptake by

  16. PCB's take a stroll Los PCBs salen de paseo

    Directory of Open Access Journals (Sweden)

    N. Olea Serrano

    2002-12-01

    Full Text Available Human exposure to bioaccumulable organochlorine compounds is a reality, not only because of the known presence in tissues of the residue of historic contaminants such as DDT and other pesticides, but also because of the risk of current exposure to compounds still in use, such as lindane, endosulphan and polychlorinated biphenyls or PCBs, among others. The case of the PCBs is of particular importance. Although their production was prohibited due to their hazardous nature, persistence and environmental toxicity, a large number of equipments that contain considerable volumes of PCBs continue functioning. These equipments will reach the residual stage in the next few years, if not already, so that their correct disposal is necessary to avoid their release into the environment. A National Plan for the decontamination and elimination of polychlorobiphenyls (PCBs, polychloroterphenyls (PCTs and the equipments that contain them was launched in Spain in 2001. This plan must be implemented taking full account of the possible effects of PBCs on the environment and human health and with the knowledge of those responsible for public health.La exposición humana a compuestos organoclorados bioacumulables es un problema de interés sanitario no sólo por el conocimiento de la presencia en tejidos del residuo de contaminantes históricos como DDT y otros pesticidas, sino por el riesgo de exposición actual a compuestos aún en uso como el lindano, el endosulfán y los bifenilos policlorados (PCBs, entre otros. Destaca el caso particular de los PCBs, sustancias cuya producción fue prohibida debido a su peligrosidad, persistencia y toxicidad ambiental. A pesar de esta prohibición siguen funcionando una gran cantidad de aparatos que contienen volúmenes considerables de PCBs. Estos aparatos llegarán en los próximos años, si no lo han hecho ya, a la fase de residuos, por lo que es necesario asegurar su correcta eliminación para evitar su liberación al medio

  17. Health Effects of PCBs in Residences and Schools (HESPERUS)

    DEFF Research Database (Denmark)

    Bräuner, Elvira; Andersen, Zorana Jovanovic; Frederiksen, Marie

    2016-01-01

    Polychlorinated-biphenyls (PCBs) were introduced in the late 1920s and used until the 1970s when they were banned in most countries due to evidence of environmental build-up and possible adverse health effects. However they still persist in the environment, indoors and in humans. Indoor air...... in contaminated buildings may confer airborne exposure markedly above background regional PCB levels. To date, no epidemiological studies have assessed the health effects from exposure to semi-volatile PCBs in the indoor environment. Indoor air PCBs are generally less chlorinated than PCBs that are absorbed via...... the diet, or via past occupational exposure; therefore their health effects require separate risk assessment. Two separate cohorts of individuals who have either attended schools (n = 66,769; 26% exposed) or lived in apartment buildings (n = 37,185; 19% exposed), where indoor air PCB concentrations have...

  18. Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

    Science.gov (United States)

    Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

    2013-01-01

    Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

  19. The Roles of Dopamine D1 Receptor on the Social Hierarchy of Rodents and Nonhuman Primates.

    Science.gov (United States)

    Yamaguchi, Yoshie; Lee, Young-A; Kato, Akemi; Goto, Yukiori

    2017-04-01

    Although dopamine has been suggested to play a role in mediating social behaviors of individual animals, it is not clear whether such dopamine signaling contributes to attributes of social groups such as social hierarchy. In this study, the effects of the pharmacological manipulation of dopamine D1 receptor function on the social hierarchy and behavior of group-housed mice and macaques were investigated using a battery of behavioral tests. D1 receptor blockade facilitated social dominance in mice at the middle, but not high or low, social rank in the groups without altering social preference among mates. In contrast, the administration of a D1 receptor antagonist in a macaque did not affect social dominance of the drug-treated animal; however, relative social dominance relationships between the drug-treated and nontreated subjects were altered indirectly through alterations of social affiliative relationships within the social group. These results suggest that dopamine D1 receptor signaling may be involved in social hierarchy and social relationships within a group, which may differ between rodents and primates. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  20. Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine.

    Directory of Open Access Journals (Sweden)

    Dawn Thompson

    Full Text Available BACKGROUND: Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R availability in the brain. Such a decrease consequently alters the ratio of D1R:D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified. METHODS AND FINDINGS: ETHICS STATEMENT: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT and G protein coupled receptor associated sorting protein-1 (GASP-1 knock out (KO mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine. CONCLUSIONS: Together, our data suggests that changes in the ratio of the D1:D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization.

  1. Firing properties of dopamine neurons in freely moving dopamine-deficient mice: Effects of dopamine receptor activation and anesthesia

    OpenAIRE

    Robinson, Siobhan; Smith, David M.; Mizumori, Sheri J. Y.; Palmiter, Richard D.

    2004-01-01

    To examine the regulation of midbrain dopamine neurons, recordings were obtained from single neurons of freely moving, genetically engineered dopamine-deficient (DD) mice. DD mice were tested without dopamine signaling (basal state) and with endogenous dopamine signaling (after L-dopa administration). In the basal state, when dopamine concentration in DD mice is

  2. Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

    Science.gov (United States)

    Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.

    2013-01-01

    Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

  3. Homeostatic mechanisms in dopamine synthesis and release: a mathematical model

    Directory of Open Access Journals (Sweden)

    Nijhout H Frederik

    2009-09-01

    Full Text Available Abstract Background Dopamine is a catecholamine that is used as a neurotransmitter both in the periphery and in the central nervous system. Dysfunction in various dopaminergic systems is known to be associated with various disorders, including schizophrenia, Parkinson's disease, and Tourette's syndrome. Furthermore, microdialysis studies have shown that addictive drugs increase extracellular dopamine and brain imaging has shown a correlation between euphoria and psycho-stimulant-induced increases in extracellular dopamine 1. These consequences of dopamine dysfunction indicate the importance of maintaining dopamine functionality through homeostatic mechanisms that have been attributed to the delicate balance between synthesis, storage, release, metabolism, and reuptake. Methods We construct a mathematical model of dopamine synthesis, release, and reuptake and use it to study homeostasis in single dopaminergic neuron terminals. We investigate the substrate inhibition of tyrosine hydroxylase by tyrosine, the consequences of the rapid uptake of extracellular dopamine by the dopamine transporters, and the effects of the autoreceoptors on dopaminergic function. The main focus is to understand the regulation and control of synthesis and release and to explicate and interpret experimental findings. Results We show that the substrate inhibition of tyrosine hydroxylase by tyrosine stabilizes cytosolic and vesicular dopamine against changes in tyrosine availability due to meals. We find that the autoreceptors dampen the fluctuations in extracellular dopamine caused by changes in tyrosine hydroxylase expression and changes in the rate of firing. We show that short bursts of action potentials create significant dopamine signals against the background of tonic firing. We explain the observed time courses of extracellular dopamine responses to stimulation in wild type mice and mice that have genetically altered dopamine transporter densities and the observed

  4. Dopamine controls Parkinson's tremor by inhibiting the cerebellar thalamus

    NARCIS (Netherlands)

    Dirkx, M.F.M.; Ouden, H.E.M. den; Aarts, E.; Timmer, M.H.M.; Bloem, B.R.; Toni, I.; Helmich, R.C.G.

    2017-01-01

    Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic

  5. The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications.

    Science.gov (United States)

    Felger, Jennifer C

    Studies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have consistently reported evidence that inflammatory cytokines affect the basal ganglia and dopamine to mediate depressive symptoms related to motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal responses to hedonic reward, decreased dopamine and dopamine metabolites in cerebrospinal fluid, and decreased availability of striatal dopamine, all of which correlate with symptoms of anhedonia, fatigue, and psychomotor retardation. Similar relationships between alterations in dopamine-relevant corticostriatal reward circuitry and symptoms of anhedonia and psychomotor slowing have also been observed in patients with major depression who exhibit increased peripheral cytokines and other inflammatory markers, such as C-reactive protein. Of note, these inflammation-associated depressive symptoms are often difficult to treat in patients with medical illnesses or major depression. Furthermore, a wealth of literature suggests that inflammation can decrease dopamine synthesis, packaging, and release, thus sabotaging or circumventing the efficacy of standard antidepressant treatments. Herein, the mechanisms by which inflammation and cytokines affect dopamine neurotransmission are discussed, which may provide novel insights into treatment of inflammation-related behavioral symptoms that contribute to an inflammatory malaise.

  6. Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

    International Nuclear Information System (INIS)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and 3 H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by α-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S 2 episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. 3 H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system

  7. The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue.

    Directory of Open Access Journals (Sweden)

    Ralf eBrisch

    2014-05-01

    Full Text Available Abstract: Dopamine is an inhibitory neurotransmitter involved in the pathology of schizophrenia.The revised dopamine hypothesis states that dopamine abnormalities in the mesolimbic and prefrontal brain regions exist in schizophrenia. However, recent research has indicated that glutamate, GABA, acetylcholine, and serotonin alterations are also involved in the pathology of schizophrenia. This review provides an in-depth analysis of dopamine in animal models of schizophrenia and also focuses on dopamine and cognition. Furthermore, this review provides not only an overview of dopamine receptors and the antipsychotic effects of treatments targeting them, but also an outline of dopamine and it`s interaction with other neurochemical models of schizophrenia. The roles of dopamine in the evolution of the human brain and human mental abilities, which are affected in schizophrenia patients, are also discussed.

  8. Dopamine alleviates nutrient deficiency-induced stress in Malus hupehensis.

    Science.gov (United States)

    Liang, Bowen; Li, Cuiying; Ma, Changqing; Wei, Zhiwei; Wang, Qian; Huang, Dong; Chen, Qi; Li, Chao; Ma, Fengwang

    2017-10-01

    Dopamine mediates many physiological processes in plants. We investigated its role in regulating growth, root system architecture, nutrient uptake, and responses to nutrient deficiencies in Malus hupehensis Rehd. Under a nutrient deficiency, plants showed significant reductions in growth, chlorophyll concentrations, and net photosynthesis, along with disruptions in nutrient uptake, transport, and distribution. However, pretreatment with 100 μM dopamine markedly alleviated such inhibitions. Supplementation with that compound enabled plants to maintain their photosynthetic capacity and development of the root system while promoting the uptake of N, P, K, Ca, Mg, Fe, Mn, Cu, Zn, and B, altering the way in which those nutrients were partitioned throughout the plant. The addition of dopamine up-regulated genes for antioxidant enzymes involved in the ascorbate-glutathione cycle (MdcAPX, MdcGR, MdMDHAR, MdDHAR-1, and MdDHAR-2) but down-regulated genes for senescence (SAG12, PAO, and MdHXK). These results indicate that exogenous dopamine has an important antioxidant and anti-senescence effect that might be helpful for improving nutrient uptake. Our findings demonstrate that dopamine offers new opportunities for its use in agriculture, especially when addressing the problem of nutrient deficiencies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques

    Science.gov (United States)

    Siciliano, Cody A.; Calipari, Erin S.; Yorgason, Jordan T.; Lovinger, David M.; Mateo, Yolanda; Jimenez, Vanessa A.; Helms, Christa M.; Grant, Kathleen A.; Jones, Sara R.

    2016-01-01

    Rationale Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use, and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are unknown. Objective Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Methods Female rhesus macaques completed one year of daily (22 hr/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa-opioid receptor agonist) induced inhibition of dopamine release. Results Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa-opioid receptors, which both act as negative regulators of presynaptic dopamine release, were moderately and robustly enhanced in ethanol drinkers. Conclusions Greater uptake rates and sensitivity to D2-type autoreceptor and kappa-opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system, and suggest that the dopamine and dynorphin/kappa-opioid receptor systems may be efficacious pharmcotherapeutic targets in the treatment of alcohol use disorders. PMID:26892380

  10. Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques.

    Science.gov (United States)

    Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T; Lovinger, David M; Mateo, Yolanda; Jimenez, Vanessa A; Helms, Christa M; Grant, Kathleen A; Jones, Sara R

    2016-04-01

    Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are not fully understood. Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Female rhesus macaques completed 1 year of daily (22 h/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa opioid receptor agonist) induced inhibition of dopamine release. Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa opioid receptors, which both act as negative regulators of presynaptic dopamine release, was moderately and robustly enhanced in ethanol drinkers. Greater uptake rates and sensitivity to D2-type autoreceptor and kappa opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system and suggest that the dopamine and dynorphin/kappa opioid receptor systems may be efficacious pharmacotherapeutic targets in the treatment of alcohol use disorders.

  11. PCDD/Fs, dioxin-like PCBs and marker PCBs in eggs of peregrine falcons from Germany

    Energy Technology Data Exchange (ETDEWEB)

    Malisch, R.; Baum, F. [CVUA, Freiburg (Germany)

    2004-09-15

    Adverse effects of persistent organochlorine pesticides (POPs) on wildlife have been widely documented in the literature. For birds, the reproductive cycle is negatively influenced. Therefore, bird's eggs are frequently used to monitor the contamination of the environment with xenobiotic substances. A high content of PCBs and p,p'-DDE (as main metabolite of p,p'-DDT) was found in eggs of peregrine falcons collected between 1988 and 1993 in the German ''Bundesland'' Baden- Wuerttemberg. Many other publications presented results for organochlorine pesticides, indicator PCBs or organobromine compounds in various bird's eggs. PCDD/Fs and dioxin-like PCBs were determined in eggs of California peregrine falcons, of cormorants in Japan, of predatory birds in Spain, of common terns in Michigan, USA, of peregrine falcons in Spain (vii) and of different sorts of hawks in Germany. The Stockholm Convention is a global treaty signed now by 55 parties to take action against certain POPs, among them PCBs, PCDDs and PCDFs. After ratification by France as the 50th Party, the Convention entered into force on 17 May 2004. The effectiveness should be evaluated four years after the date of entry into force and periodically thereafter at intervals. Therefore, a Global POPs Monitoring Programme was developed. United Nations Environment Programme (UNEP) organized a workshop to provide a scientific basis for this programme. One of the conclusions was to select the following matrices: air; bivalves; wildlife species (fish, bird's eggs, marine mammals) and human milk. The main reason for inclusion wildlife including bird's eggs was to gain information on temporal trends on, at the least, a regional basis, in animals, which represent either top predators or important species within aquatic or terrestrial food chains. For falcons, a high accumulation of POPs was observed. Regarding the migration habits it is known that older peregrine falcons

  12. Review of chemical and electrokinetic remediation of PCBs contaminated soils and sediments.

    Science.gov (United States)

    Fan, Guangping; Wang, Yu; Fang, Guodong; Zhu, Xiangdong; Zhou, Dongmei

    2016-09-14

    Polychlorinated biphenyls (PCBs) are manmade organic compounds, and pollution due to PCBs has been a global environmental problem because of their persistence, long-range atmospheric transport and bioaccumulation. Many physical, chemical and biological technologies have been utilized to remediate PCBs contaminated soils and sediments, and there are some emerging new technologies and combined methods that may provide cost-effective alternatives to the existing remediation practice. This review provides a general overview on the recent developments in chemical treatment and electrokinetic remediation (EK) technologies related to PCBs remediation. In particular, four technologies including photocatalytic degradation of PCBs combined with soil washing, Fe-based reductive dechlorination, advanced oxidation process, and EK/integrated EK technology (e.g., EK coupled with chemical oxidation, nanotechnology and bioremediation) are reviewed in detail. We focus on the fundamental principles and governing factors of chemical technologies, and EK/integrated EK technologies. Comparative analysis of these technologies including their major advantages and disadvantages is summarized. The existing problems and future prospects of these technologies regarding PCBs remediation are further highlighted.

  13. Maternal separation affects dopamine transporter function in the Spontaneously Hypertensive Rat: An in vivo electrochemical study

    Directory of Open Access Journals (Sweden)

    Womersley Jacqueline S

    2011-12-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT in ways that distinguish SHR from control rat strains. Methods SHR and control Wistar-Kyoto (WKY rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Results Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1 in SHR striatum. Consistent with this observation, the dopamine clearance time (T100 was increased in SHR. These results suggest that the chronic mild stress of

  14. Correlations between dioxin-like and indicators PCBs: Potential consequences for environmental studies involving fish or sediment

    International Nuclear Information System (INIS)

    Babut, M.; Miege, C.; Villeneuve, B.; Abarnou, A.; Duchemin, J.; Marchand, P.; Narbonne, J.F.

    2009-01-01

    Among the numerous PCB congeners, most of the dioxin-like PCBs (DL-PCBs) need to be characterized by hyphenated techniques. It has been shown in several instances that these congeners are well related to the total PCB content in fish. We examined datasets collected mainly in France, on freshwater and marine fish and sediments. A statistical model linking DL- and indicator PCBs was developed for a dataset composed of freshwater fishes, and proved to predict well DL-PCBs from indicator PCBs in all other fish sets, including marine ones. Type II error rates remained low in almost all fish sets. A similar correlation was observed in sediments. Non-dioxin-like PCBs elicit various adverse effects and represent 95% of the total PCBs. A European guideline for them is needed; the correlation between DL- and indicator PCBs could help develop this standard in the future. - Dioxin-like PCBs in fish and maybe sediments are rather well predicted by indicator PCBs.

  15. Dopamine receptors on adrenal chromaffin cells modulate calcium uptake and catecholamine release

    Energy Technology Data Exchange (ETDEWEB)

    Bigornia, L; Suozzo, M; Ryan, K A; Napp, D; Schneider, A S

    1988-10-01

    The presence of dopamine-containing cells in sympathetic ganglia, i.e., small, intensely fluorescent cells, has been known for some time. However, the role of dopamine as a peripheral neurotransmitter and its mechanism of action are not well understood. Previous studies have demonstrated the presence of D2 dopamine receptors on the surface of bovine adrenal chromaffin cells using radioligand binding methods and dopamine receptor inhibition of catecholamine release from perfused adrenal glands. In the present study, we provide evidence confirming a role of dopamine receptors as inhibitory modulators of adrenal catecholamine release from bovine chromaffin cell cultures and further show that the mechanism of modulation involves inhibition of stimulated calcium uptake. Apomorphine gave a dose-dependent inhibition (IC50 = 1 microM) of 45Ca2+ uptake stimulated by either nicotine (10 microM) or membrane depolarization with an elevated K+ level (60 mM). This inhibition was reversed by a series of specific (including stereospecific) dopamine receptor antagonists: haloperidol, spiperone, sulpiride, and (+)-butaclamol, but not (-)-butaclamol. In addition, the calcium channel agonist Bay K 8644 was used to stimulate uptake of 45Ca2+ into chromaffin cells, and this uptake was also inhibited by the dopamine receptor agonist apomorphine. The combined results suggest that dopamine receptors on adrenal chromaffin cells alter Ca2+ channel conductance, which, in turn, modulates catecholamine release.

  16. Attenuation of antagonist-induced impairment of dopamine receptors by L-prolyl-L-leucyl-glycinamide

    International Nuclear Information System (INIS)

    Saleh, M.I.M.

    1988-01-01

    The present study was undertaken in order to determine whether chronic,long-term postnatal challenge of rat pups per se, with specific dopamine D1 and D2 receptor antagonists, would modify the ontogeny of the respective receptor types. Since the neuropeptide L-prolyl-L-leucyl-glycinamide (PLG) attenuates the effect of haloperidol on dopamine D2 receptors in adult rats it was of interest to determine whether PLG would modulate antagonists-induced alterations in the ontogeny of striatal dopamine D1 and D2 receptors. Half of the rats were treated daily for 32 days from birth with SCH-23390, a selective dopamine D1 antagonist; or spiroperidol, a selective dopamine D2 antagonists; or both SCH-23390 and spiroperidol; or saline. The other half of the litters were treated with PLG, in combination with the other treatments. Animals were decapitated at 5, 8, and 12 weeks from birth for neurochemical analysis of the striatum. Chronic SCH-23390 treatment produced a 70-80% decrease in the binding of [ 3 H] SCH-23390 to striatal homogenates. The alteration at 5 weeks was associated with a 78% decrease in the Bmax for [ 3 H] SCH-23390 binding, and no change in the K D . Similarly, at 5, 8, and 12 weeks, chronic spiroperidol treatment reduced the binding of [ 3 H] spiroperidol to striatal homogenates by 70-80%

  17. Dopamine synthesis in alcohol drinking-prone and -resistant mouse strains

    Science.gov (United States)

    Siciliano, Cody A.; Locke, Jason L.; Mathews, Tiffany A.; Lopez, Marcelo F.; Becker, Howard C.; Jones, Sara R.

    2017-01-01

    Alcoholism is a prevalent and debilitating neuropsychiatric disease, and much effort has been aimed at elucidating the neurobiological mechanisms underlying maladaptive alcohol drinking in an effort to design rational treatment strategies. In preclinical literature, the use of inbred mouse lines has allowed for the examination of ethanol effects across vulnerable and resistant phenotypes. C57BL/6J mice consistently show higher rates of ethanol drinking compared to most mouse strains. Conversely, DBA/2J mice display low rates of ethanol consumption. Given that the reinforcing and rewarding effects of ethanol are thought to be in part mediated by its actions on dopamine neurotransmission, we hypothesized that alcohol-preferring C57BL/6J and alcohol-avoiding DBA/2J mice would display basal differences in dopamine system function. By administering an L-aromatic acid decarboxylase inhibitor and measuring L-Dopa accumulation via high-performance liquid chromatography as a measure of tyrosine hydroxylase activity, we found no difference in dopamine synthesis between mouse strains in the midbrain, dorsal striatum, or ventral striatum. However, we did find that quinpirole-induced inhibition of dopamine synthesis was greater in the ventral striatum of C57BL/6J mice, suggesting increased presynaptic D2-type dopamine autoreceptor sensitivity. To determine whether dopamine synthesis or autoreceptor sensitivity was altered by a history of ethanol, we exposed C57BL/6J mice to one or two weekly cycles of chronic intermittent ethanol (CIE) exposure and withdrawal. We found that there was an attenuation of baseline dopamine synthesis in the ventral striatum after two cycles of CIE. Finally, we examined tissue content of dopamine and dopamine metabolites across recombinant inbred mice bred from a C57BL/6J × DBA/2J cross (BXD). We found that low dopaminergic activity, as indicated by high dopamine/metabolite ratios, was positively correlated with drinking. Together, these findings

  18. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.

    Science.gov (United States)

    Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno

    2015-03-15

    Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

    Energy Technology Data Exchange (ETDEWEB)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and /sup 3/H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by ..cap alpha..-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S/sub 2/ episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. /sup 3/H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system.

  20. Occurrence, bioaccumulation and risk assessment of dioxin-like PCBs along the Chenab river, Pakistan

    International Nuclear Information System (INIS)

    Eqani, Syed Ali Musstjab Akber Shah; Cincinelli, Alessandra; Mehmood, Adeel; Malik, Riffat Naseem; Zhang, Gan

    2015-01-01

    This study aimed to assess the occurrence, distribution and dietary risks of seven dl-PCBs (dioxin-like PCBs) in eleven collected fish species from Chenab river, Pakistan. ∑_7dl-PCBs (ng g"−"1, wet weight) burden was species-specific and the maximum average concentrations were found in Mastacembelus armatus (5.43), and Rita rita (5.1). Correlation of each dl-PCBs with δ"1"5N%, indicated a food chain accumulation process of these chemicals into Chenab river, Pakistan. Species-specific toxicity of each dl-PCBs (WHO–PCBs TEQ) was calculated and higher values were found in three carnivore fish species i.e., M. armatus (2.5 pg TEQ g"−"1), R. rita (2.47 pg TEQ g"−"1), Securicola gora (2.98 pg TEQ g"−"1) and herbivore fish species i.e., Cirrhinus mrigala (2.44 pg TEQ g"−"1). The EDI (Estimated Daily Intake) values in most cases exceeded the WHO benchmark (4 pg WHO–TEQ kg"−"1 bw d"−"1) evidencing a potential health risk for consumers via fish consumption from Chenab river. - Highlights: • Dioxin-like PCBs in eleven collected fish species from Chenab river. • ∑_7dl-PCBs (ng/g, ww) burdens were specie-specific. • dl-PCBs (WHO-pg TEQ g"−"1ww) ranged between 0.96 and 2.9 in fish samples. • PCB-126 contribution was predominant towards total WHO dl-PCB TEQs. • Potential human health risk of dl-PCBs via fish consumption from Chenab river. - ∑_7dl-PCBs (ng g"−"1, ww) burdens in collected fish species from Chenab river, Pakistan reflected the potential human health risk via fish consumption.

  1. Desorption, partitioning, and dechlorination characteristics of PCBs in sediments in interaction with reactive activated carbon

    International Nuclear Information System (INIS)

    Choi, Hyeok; Lawal, Wasiu; Al-Abed, Souhail R.

    2015-01-01

    Highlights: • Problematic aged real PCBs-contaminated sediment (WHS) was examined. • Performance of reactive activated carbon (RAC) impregnated with Pd–ZVI was tested. • Fate and transport of PCBs bound to WHS in the presence of RAC was fully traced. • Direct mixing configuration was compared with compartment configuration. • Results reflected real world complexities associated with slow desorption of PCBs. - Abstract: Sediment (WHS) in Waukegan Harbor, Illinois, heavily contaminated and aged with polychlorinated biphenyls (PCBs), was treated with reactive activated carbon (RAC) impregnated with palladized iron nanoparticles. Lab test proceeded in a direct mixing configuration of RAC and WHS. A compartment configuration, where RAC was physically separated from WHS, was also designed to trace the sequential transport and fate of PCBs, including desorption, adsorption, dechlorination, and re-partitioning. PCBs, once desorbed from WHS, were immediately sequestrated to RAC and subject to dechlorination. Direct mixing of WHS with RAC was one-order of magnitude more effective for dechlorination than compartment configuration. Compared to their desorption-followed by-adsorption route, direct physical contact of RAC with PCBs bound to WHS exhibited negligible contribution to the availability of PCBs for dechlorination reaction. Addition of RAC even in compartment configuration facilitated PCBs desorption from WHS. However, slow desorption of PCBs limited overall performance, resulting in a five-order of magnitude lower dechlorination yield when compared with treatment of purely aqueous PCBs. The low dechlorination yield reflected real world complexities in treating 3.19% organic carbon-containing WHS aged with PCBs for 40 years. These observations were further supported when compared with results on clean Cesar Creek sediment spiked with 2-chlorinated biphenyls

  2. Desorption, partitioning, and dechlorination characteristics of PCBs in sediments in interaction with reactive activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyeok, E-mail: hchoi@uta.edu [Department of Civil Engineering, The University of Texas at Arlington, 416 Yates Street, Arlington, TX 76019-0308 (United States); Environmental and Earth Sciences Program, The University of Texas at Arlington, 500 Yates Street, Arlington, TX 76019-0049 (United States); Lawal, Wasiu [Environmental and Earth Sciences Program, The University of Texas at Arlington, 500 Yates Street, Arlington, TX 76019-0049 (United States); Al-Abed, Souhail R. [National Risk Management Research Laboratory, U.S. Environmental Protection Agency, 26 W. Martin Luther King Dr., Cincinnati, OH 45268 (United States)

    2015-04-28

    Highlights: • Problematic aged real PCBs-contaminated sediment (WHS) was examined. • Performance of reactive activated carbon (RAC) impregnated with Pd–ZVI was tested. • Fate and transport of PCBs bound to WHS in the presence of RAC was fully traced. • Direct mixing configuration was compared with compartment configuration. • Results reflected real world complexities associated with slow desorption of PCBs. - Abstract: Sediment (WHS) in Waukegan Harbor, Illinois, heavily contaminated and aged with polychlorinated biphenyls (PCBs), was treated with reactive activated carbon (RAC) impregnated with palladized iron nanoparticles. Lab test proceeded in a direct mixing configuration of RAC and WHS. A compartment configuration, where RAC was physically separated from WHS, was also designed to trace the sequential transport and fate of PCBs, including desorption, adsorption, dechlorination, and re-partitioning. PCBs, once desorbed from WHS, were immediately sequestrated to RAC and subject to dechlorination. Direct mixing of WHS with RAC was one-order of magnitude more effective for dechlorination than compartment configuration. Compared to their desorption-followed by-adsorption route, direct physical contact of RAC with PCBs bound to WHS exhibited negligible contribution to the availability of PCBs for dechlorination reaction. Addition of RAC even in compartment configuration facilitated PCBs desorption from WHS. However, slow desorption of PCBs limited overall performance, resulting in a five-order of magnitude lower dechlorination yield when compared with treatment of purely aqueous PCBs. The low dechlorination yield reflected real world complexities in treating 3.19% organic carbon-containing WHS aged with PCBs for 40 years. These observations were further supported when compared with results on clean Cesar Creek sediment spiked with 2-chlorinated biphenyls.

  3. Extracellular dopamine, acetylcholine, and activation of dopamine D1 and D2 receptors after selective breeding for cocaine self-administration in rats.

    Science.gov (United States)

    Xu, Haiyang; Das, Sasmita; Sturgill, Marc; Hodgkinson, Colin; Yuan, Qiaoping; Goldman, David; Grasing, Kenneth

    2017-08-01

    The low self-administration (LS)/Kgras (LS) and high self-administration (HS)/Kgras (HS) rat lines were generated by selective breeding for low- and high-intravenous cocaine self-administration, respectively, from a common outbred Wistar stock (Crl:WI). This trait has remained stable after 13 generations of breeding. The objective of the present study is to compare cocaine preference, neurotransmitter release, and dopamine receptor activation in LS and HS rats. Levels of dopamine, acetylcholine, and cocaine were measured in the nucleus accumbens (NA) shell of HS and LS rats by tandem mass spectrometry of microdialysates. Cocaine-induced locomotor activity and conditioned-place preference were compared between LS and HS rats. HS rats displayed greater conditioned-place preference scores compared to LS and reduced basal extracellular concentrations of dopamine and acetylcholine. However, patterns of neurotransmitter release did not differ between strains. Low-dose cocaine increased locomotor activity in LS rats, but not in HS animals, while high-dose cocaine augmented activity only in HS rats. Either dose of cocaine increased immunoreactivity for c-Fos in the NA shell of both strains, with greater elevations observed in HS rats. Activation identified by cells expressing both c-Fos and dopamine receptors was generally greater in the HS strain, with a similar pattern for both D1 and D2 dopamine receptors. Diminished levels of dopamine and acetylcholine in the NA shell, with enhanced cocaine-induced expression of D1 and D2 receptors, are associated with greater rewarding effects of cocaine in HS rats and an altered dose-effect relationship for cocaine-induced locomotor activity.

  4. Enhanced PCBs sorption on biochars as affected by environmental factors: Humic acid and metal cations

    International Nuclear Information System (INIS)

    Wang Yu; Wang Lei; Fang Guodong; Herath, H.M.S.K.; Wang Yujun; Cang Long; Xie Zubin; Zhou Dongmei

    2013-01-01

    Biochar plays an important role in the behaviors of organic pollutants in the soil environment. The role of humic acid (HA) and metal cations on the adsorption affinity of polychlorinated biphenyls (PCBs) to the biochars in an aqueous medium and an extracted solution from a PCBs-contaminated soil was studied using batch experiments. Biochars were produced with pine needles and wheat straw at 350 °C and 550 °C under anaerobic condition. The results showed that the biochars had high adsorption affinity for PCBs. Pine needle chars adsorbed less nonplanar PCBs than planar ones due to dispersive interactions and separation. Coexistence of HA and metal cations increased PCBs sorption on the biochars accounted for HA adsorption and cation complexation. The results will aid in a better understanding of biochar sorption mechanism of contaminants in the environment. - Highlights: ► Application of the biochars for PCBs sorption was a new and effective way. ► The biochars had higher adsorption affinity for PCBs in the soil extracted solution. ► Pine needle chars adsorbed less nonplanar PCBs than planar ones. ► Coexisting humic acid or metal cations increased PCBs sorption on the biochars. - The biochars had higher adsorption affinity for PCBs in the extracted soil solution because coexisting humic acid and metal cations increased their sorption.

  5. PCDD/F, dioxin-like and markers PCBs in trouts from French aquaculture

    Energy Technology Data Exchange (ETDEWEB)

    Marchand, P.; Matayron, G.; Gade, C.; Le Bizec, B.; Andre, F. [LABERCA-ENVN, Nantes (France)

    2004-09-15

    Since the introduction of 12 ''dioxin-like'' polychlorinated biphenyls (PCBs) into the assessment of a tolerable daily intake (TDI) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) by the World Health Organization (WHO) in 1998, the analytical determination of nonand mono-ortho PCBs is of increasing interest in the scientific community. The European Commission has already published a regulation that sets maximum limits for dioxins in foodstuffs (Council Regulation 2375/01/EC amending Commission regulation (EC) N 466/2001 setting maximum levels for certain contaminants in foodstuffs). As an additional feature of the reduction strategy for this group of compounds, the European Commission has planned to include the dioxinlike PCBs in the limit values for food and feeding stuffs starting at the end of 2004. The LABERCA (French National Reference Laboratory for dioxins and dioxin-like PCBs (DL-PCBs)) and the CIPA (French Interprofessional Committee for Aquaculture products) reported levels in French farmed trout according to WHO-TEQ expression and sum of Markers PCBs (m-PCBs). It must be emphasized that this survey only represents a snapshot in time. The results cannot be used to determine the potential contamination of other batches that have not been tested. However, the fish samples were taken from 58 aquaculture sites and 10 fishes were pooled from each site. It is the reason why the results can be interpreted as a good indicative of the contamination levels in farmed trout produced in France.

  6. Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders.

    Science.gov (United States)

    Baskerville, Tracey A; Douglas, Alison J

    2010-06-01

    Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a

  7. Dopamine and serotonin: influences on male sexual behavior.

    Science.gov (United States)

    Hull, Elaine M; Muschamp, John W; Sato, Satoru

    2004-11-15

    Steroid hormones regulate sexual behavior primarily by slow, genomically mediated effects. These effects are realized, in part, by enhancing the processing of relevant sensory stimuli, altering the synthesis, release, and/or receptors for neurotransmitters in integrative areas, and increasing the responsiveness of appropriate motor outputs. Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation. Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT(2C) receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins. One means for this inhibition is a decrease in dopamine release in the mesolimbic tract.

  8. Interspecies variability of Dioxin-like PCBs accumulation in five plants from the modern Yellow River delta

    International Nuclear Information System (INIS)

    Fan Guolan; Cui Zhaojie; Liu Jing

    2009-01-01

    To investigate the interspecies variance of Dioxin-like polychlorinated biphenyls (DL-PCBs) in the plants from modern Yellow River delta, the concentrations of 12 DL-PCBs congeners were examined in five plant species and their associated soils. The DL-PCBs concentrations in plants (2.32-287.60 ng/kg dry weight) were low compared to most published literature, and the concentrations and ratios of DL-PCBs congeners in plants varied greatly among species. The properties of plants and PCBs were then studied to explore the factors affecting the interspecies variance of DL-PCBs accumulation. The plants with the smallest variance of morphological and physiological characteristics (Imperata cylindrical var. Major and Phragmites australis (Cav.) Trin. ex Steud) had the most similar accumulation patterns of DL-PCBs among the species tested. As the octanol-air partitioning coefficient (K oa ) of the DL-PCBs increased, interspecies variance decreased on the whole plant level. Interestingly, the correlation between the DL-PCBs concentrations in plants and log K oa of congeners was found to be significant for annual plants, but for perennial plants it was not significant. Thus the patterns of uptake of DL-PCBs are different between annual and perennial plants

  9. Interspecies variability of Dioxin-like PCBs accumulation in five plants from the modern Yellow River delta

    Energy Technology Data Exchange (ETDEWEB)

    Guolan, Fan [Environmental Research Institute, Shandong University, Jinan, Shandong Province 250100 (China); Cui Zhaojie [School of Environmental Science and Engineering, Shandong University, Jinan, Shandong Province 250100 (China)], E-mail: cuizj@sdu.edu.cn; Jing, Liu [School of City Planning and Environmental Engineering, Shandong Jianzhu University, Jinan, Shandong Province 250101 (China)

    2009-04-30

    To investigate the interspecies variance of Dioxin-like polychlorinated biphenyls (DL-PCBs) in the plants from modern Yellow River delta, the concentrations of 12 DL-PCBs congeners were examined in five plant species and their associated soils. The DL-PCBs concentrations in plants (2.32-287.60 ng/kg dry weight) were low compared to most published literature, and the concentrations and ratios of DL-PCBs congeners in plants varied greatly among species. The properties of plants and PCBs were then studied to explore the factors affecting the interspecies variance of DL-PCBs accumulation. The plants with the smallest variance of morphological and physiological characteristics (Imperata cylindrical var. Major and Phragmites australis (Cav.) Trin. ex Steud) had the most similar accumulation patterns of DL-PCBs among the species tested. As the octanol-air partitioning coefficient (K{sub oa}) of the DL-PCBs increased, interspecies variance decreased on the whole plant level. Interestingly, the correlation between the DL-PCBs concentrations in plants and log K{sub oa} of congeners was found to be significant for annual plants, but for perennial plants it was not significant. Thus the patterns of uptake of DL-PCBs are different between annual and perennial plants.

  10. Bioremediation of PCBs. CRADA final report

    International Nuclear Information System (INIS)

    Klasson, K.T.; Abramowicz, D.A.

    1996-06-01

    The Cooperative Research and Development Agreement was signed between Oak Ridge National Laboratory (ORNL) and General Electric Company (GE) on August 12, 1991. The objective was a collaborative venture between researchers at GE and ORNL to develop bioremediation of polychlorinated biphenyls (PCBs). The work was conducted over three years, and this report summarizes ORNL's effort. It was found that the total concentration of PCBs decreased by 70% for sequential anaerobic-aerobic treatment compared with a 67% decrease for aerobic treatment alone. The sequential treatment resulted in PCB products with fewer chlorines and shorter halflives in humans compared with either anaerobic or aerobic treatment alone. The study was expected to lead to a technology applicable to a field experiment that would be performed on a DOE contaminated site

  11. Developmental Vitamin D (DVD) Deficiency Reduces Nurr1 and TH Expression in Post-mitotic Dopamine Neurons in Rat Mesencephalon.

    Science.gov (United States)

    Luan, Wei; Hammond, Luke Alexander; Cotter, Edmund; Osborne, Geoffrey William; Alexander, Suzanne Adele; Nink, Virginia; Cui, Xiaoying; Eyles, Darryl Walter

    2018-03-01

    Developmental vitamin D (DVD) deficiency has been proposed as an important risk factor for schizophrenia. Our previous study using Sprague Dawley rats found that DVD deficiency disrupted the ontogeny of mesencephalic dopamine neurons by decreasing the mRNA level of a crucial differentiation factor of dopamine cells, the nuclear receptor related 1 protein (Nurr1). However, it remains unknown whether this reflects a reduction in dopamine cell number or in Nurr1 expression. It is also unclear if any particular subset of developing dopamine neurons in the mesencephalon is selectively affected. In this study, we employed state-of-the-art spinning disk confocal microscopy optimized for the imaging of tissue sections and 3D segmentation to assess post-mitotic dopamine cells on a single-cell basis in the rat mesencephalon at embryonic day 15. Our results showed that DVD deficiency did not alter the number, morphology, or positioning of post-mitotic dopamine cells. However, the ratio of Nurr1+TH+ cells in the substantia nigra pars compacta (SNc) compared with the ventral tegmental area (VTA) was increased in DVD-deficient embryos. In addition, the expression of Nurr1 in immature dopamine cells and mature dopamine neurons in the VTA was decreased in DVD-deficient group. Tyrosine hydroxylase was selectively reduced in SNc of DVD-deficient mesencephalon. We conclude that DVD deficiency induced early alterations in mesencephalic dopamine development may in part explain the abnormal dopamine-related behaviors found in this model. Our findings may have broader implications for how certain environmental risk factors for schizophrenia may shape the ontogeny of dopaminergic systems and by inference increase the risk of schizophrenia.

  12. Uptake of PCBs contained in marine sediments by the green macroalga Ulva rigida.

    Science.gov (United States)

    Cheney, Donald; Rajic, Ljiljana; Sly, Elizabeth; Meric, Dogus; Sheahan, Thomas

    2014-11-15

    The uptake of PCBs contained in marine sediments by the green macroalga Ulva rigida was investigated in both laboratory and field experiments. Under laboratory conditions, total PCBs (tPCBs) uptake was significantly greater in live vs dead plants. The concentration of tPCB taken up in live plants was greatest in the first 24h (1580 μg kg(-1) dry weight), and then increased at a lower rate from day 2 to 14. Dead plants had a significantly lower tPCB concentration after 24h (609 μg kg(-1) dry weight) and lower uptake rate through day 14. Lesser chlorinated PCB congeners (below 123) made up the majority of PCBs taken up. Congener composition in both laboratory and field experiments was correlated to congener logKow value and sediment content. Field experiments showed that Ulva plants could concentrate PCBs to 3.9 mg kg(-1) in 24h. Thus, U. rigida is capable of removing PCBs in sediments at a rapid rate. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. War in Croatia, Bosnia and Herzegowina, and Kosovo, and PCBs hazards

    Energy Technology Data Exchange (ETDEWEB)

    Picer, M.; Kovac, T.; Picer, N.; Calic, V. [Rudjer Boskovic Inst., Zagreb (Croatia); Miosic, N. [Geological Survey, Sarajevo (Bosnia and Herzegowina); Kodba, Z.C. [Maribor Environmental Protection Inst., Maribor (Slovenia); Rugova, A. [Pristina Univ., Pristina (Serbia)

    2005-07-01

    Recent warfare in Croatia, Bosnia and Herzegowina, and Kosovo has increased hazardous waste levels in the involved regions. Data on contaminant levels from water and soil samples collected before 1995 did not demonstrate significant levels of contamination. This paper provided the results of a study which showed that significant levels of persistent organic pollutants (POPs) exist in many of the areas worst affected by the war. During the study, soil and sediment samples were extracted with n-hexane. Fish extracts were extracted using a high revolution blender. Polychlorinated biphenyls (PCBs) were then separated from organochlorine insecticides on a silica gel column. Electron capture detection gas chromatography (ECD-GC) was used to quantify the POPs. Results showed that levels of PCBs in soil samples from Bosnia and Herzegowina sampled during 2003 showed significantly high levels of total PCBs. Levels of contamination exceeded tolerance levels accepted in Netherlands. Fish samples did not demonstrate high levels of contaminants. Sediment samples from Bosnian rivers showed significant levels of PCBs. It was concluded that levels of PCBs in Bosnia and Herzegowina in 2003 were lower than levels observed in fish sampled in Dalmatia and Croatia. 5 refs., 1 tab., 3 figs.

  14. Ketogenic diet alters dopaminergic activity in the mouse cortex.

    Science.gov (United States)

    Church, William H; Adams, Ryan E; Wyss, Livia S

    2014-06-13

    The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Desorption, partitioning, and dechlorination characteristics of PCBs in sediments in interaction with reactive activated carbon.

    Science.gov (United States)

    Choi, Hyeok; Lawal, Wasiu; Al-Abed, Souhail R

    2015-04-28

    Sediment (WHS) in Waukegan Harbor, Illinois, heavily contaminated and aged with polychlorinated biphenyls (PCBs), was treated with reactive activated carbon (RAC) impregnated with palladized iron nanoparticles. Lab test proceeded in a direct mixing configuration of RAC and WHS. A compartment configuration, where RAC was physically separated from WHS, was also designed to trace the sequential transport and fate of PCBs, including desorption, adsorption, dechlorination, and re-partitioning. PCBs, once desorbed from WHS, were immediately sequestrated to RAC and subject to dechlorination. Direct mixing of WHS with RAC was one-order of magnitude more effective for dechlorination than compartment configuration. Compared to their desorption-followed by-adsorption route, direct physical contact of RAC with PCBs bound to WHS exhibited negligible contribution to the availability of PCBs for dechlorination reaction. Addition of RAC even in compartment configuration facilitated PCBs desorption from WHS. However, slow desorption of PCBs limited overall performance, resulting in a five-order of magnitude lower dechlorination yield when compared with treatment of purely aqueous PCBs. The low dechlorination yield reflected real world complexities in treating 3.19% organic carbon-containing WHS aged with PCBs for 40 years. These observations were further supported when compared with results on clean Cesar Creek sediment spiked with 2-chlorinated biphenyls. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. High fructose corn syrup induces metabolic dysregulation and altered dopamine signaling in the absence of obesity

    OpenAIRE

    Meyers, Allison M.; Mourra, Devry; Beeler, Jeff A.

    2017-01-01

    The contribution of high fructose corn syrup (HFCS) to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO) and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study ...

  17. Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases

    Directory of Open Access Journals (Sweden)

    Sven I Walaas

    2011-08-01

    Full Text Available Dopamine plays an important modulatory role in the central nervous system, helping to control critical aspects of motor function and reward learning. Alteration in normal dopaminergic neurotransmission underlies multiple neurological diseases including schizophrenia, Huntington's disease and Parkinson's disease. Modulation of dopamine-regulated signaling pathways is also important in the addictive actions of most drugs of abuse. Our studies over the last 30 years have focused on the molecular actions of dopamine acting on medium spiny neurons, the predominant neurons of the neostriatum. Striatum-enriched phosphoproteins, particularly DARPP-32, RCS (Regulator of Calmodulin Signaling and ARPP-16, mediate pleiotropic actions of dopamine. Notably, each of these proteins, either directly or indirectly, regulates the activity of one of the three major subclasses of serine/threonine protein phosphatases, PP1, PP2B and PP2A, respectively. For example, phosphorylation of DARPP-32 at Thr34 by protein kinase A results in potent inhibition of PP1, leading to potentiation of dopaminergic signaling at multiple steps from the dopamine receptor to the nucleus. The discovery of DARPP-32 and its emergence as a critical molecular integrator of striatal signaling will be discussed, as will more recent studies that highlight novel roles for RCS and ARPP-16 in dopamine-regulated striatal signaling pathways.

  18. Methamphetamine Increases Locomotion and Dopamine Transporter Activity in Dopamine D5 Receptor-Deficient Mice

    OpenAIRE

    Hayashizaki, Seiji; Hirai, Shinobu; Ito, Yumi; Honda, Yoshiko; Arime, Yosefu; Sora, Ichiro; Okado, Haruo; Kodama, Tohru; Takada, Masahiko

    2013-01-01

    Dopamine regulates the psychomotor stimulant activities of amphetamine-like substances in the brain. The effects of dopamine are mediated through five known dopamine receptor subtypes in mammals. The functional relevance of D5 dopamine receptors in the central nervous system is not well understood. To determine the functional relevance of D5 dopamine receptors, we created D5 dopamine receptor-deficient mice and then used these mice to assess the roles of D5 dopamine receptors in the behaviora...

  19. Deeper insights into PCBs in orcas

    DEFF Research Database (Denmark)

    Dietz, Rune; Eulaers, Igor; Desforges, Jean-Pierre

    2016-01-01

    Having read the recent article by Jepson and Law (DOI: 10.1126/science.aaf9075) we want to emphasise the worrying nature of the fact that at present many marine apex predators, including killer whales, remain highly polluted with PCBs despite world-wide initiatives over past decades to restrict...... PCB-containing equipment by 2025 and perform environmentally sound waste management by 2028. This means nonetheless that PCBs will continue to leach into the environment over the next decade. Given present-day observed reproductive failure in several killer whale populations we must urgently reduce...... are excellent marine sentinel species, indicating that not one nation can address the persistent threat that is environmental PCB pollution. We believe the choice for international PCB mitigation is timely in order to not lose this canary in the coalmine....

  20. Bioremediation of PCBs. CRADA final report

    Energy Technology Data Exchange (ETDEWEB)

    Klasson, K.T. [Oak Ridge National Lab., TN (United States). Chemical Technology Div., TN (United States); Abramowicz, D.A. [General Electric Co. Corporate Research and Development, Niskayuna, NY (United States)

    1996-06-01

    The Cooperative Research and Development Agreement was signed between Oak Ridge National Laboratory (ORNL) and General Electric Company (GE) on August 12, 1991. The objective was a collaborative venture between researchers at GE and ORNL to develop bioremediation of polychlorinated biphenyls (PCBs). The work was conducted over three years, and this report summarizes ORNL`s effort. It was found that the total concentration of PCBs decreased by 70% for sequential anaerobic-aerobic treatment compared with a 67% decrease for aerobic treatment alone. The sequential treatment resulted in PCB products with fewer chlorines and shorter halflives in humans compared with either anaerobic or aerobic treatment alone. The study was expected to lead to a technology applicable to a field experiment that would be performed on a DOE contaminated site.

  1. Polychlorinated biphenyls (PCBs enhance metastatic properties of breast cancer cells by activating Rho-associated kinase (ROCK.

    Directory of Open Access Journals (Sweden)

    Sijin Liu

    Full Text Available BACKGROUND: Polychlorinated biphenyls (PCBs are a family of structurally related chlorinated aromatic hydrocarbons. Numerous studies have documented a wide spectrum of biological effects of PCBs on human health, such as immunotoxicity, neurotoxicity, estrogenic or antiestrogenic activity, and carcinogenesis. The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo, animal and epidemiologic studies. A number of investigations indicated that higher levels of PCBs in mammary tissues or sera correlated to breast cancer risk, and PCBs might be implicated in advancing breast cancer progression. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, we for the first time report that PCBs greatly promote the ROCK activity and therefore increase cell motility for both non-metastatic and metastatic human breast cancer cells in vitro. In the in vivo study, PCBs significantly advance disease progression, leading to enhanced capability of metastatic breast cancer cells to metastasize to bone, lung and liver. Additionally, PCBs robustly induce the production of intracellular reactive oxygen species (ROS in breast cancer cells; ROS mechanistically elevate ROCK activity. CONCLUSIONS/SIGNIFICANCE: PCBs enhance the metastatic propensity of breast cancer cells by activating the ROCK signaling, which is dependent on ROS induced by PCBs. Inhibition of ROCK may stand for a unique way to restrain metastases in breast cancer upon PCB exposure.

  2. PCBs are associated with altered gene transcript profiles in arctic Beluga Whales (Delphinapterus leucas).

    Science.gov (United States)

    Noël, Marie; Loseto, Lisa L; Helbing, Caren C; Veldhoen, Nik; Dangerfield, Neil J; Ross, Peter S

    2014-01-01

    High trophic level arctic beluga whales (Delphinapterus leucas) are exposed to persistent organic pollutants (POP) originating primarily from southern latitudes. We collected samples from 43 male beluga harvested by Inuvialuit hunters (2008-2010) in the Beaufort Sea to evaluate the effects of POPs on the levels of 13 health-related gene transcripts using quantitative real-time polymerase chain reaction. Consistent with their role in detoxification, the aryl hydrocarbon receptor (Ahr) (r(2) = 0.18, p = 0.045 for 2008 and 2009) and cytochrome P450 1A1 (Cyp1a1) (r(2) = 0.20, p sea ice extent (2008 and 2010). δ(13)C results suggested a shift in feeding ecology and/or change in condition of these ice edge-associated beluga whales during these two years. While this provides insight into the legacy of PCBs in a remote environment, the possible impacts of a changing ice climate on the health of beluga underscores the need for long-term studies.

  3. Automated rapid analysis for dioxins and PCBs in food, feedingstuff and environmental matrices

    Energy Technology Data Exchange (ETDEWEB)

    Hoelscher, K.; Maulshagen, A.; Behnisch, P.A. [eurofins-GfA, Muenster (Germany); Shirkhan, H. [Fluid Management Systems Inc., Waltham, MA (United States); Lieck, G. [University of Applied Science, Steinfurt (Germany)

    2004-09-15

    Today there is a need to develop high throughput specific and sensitive methods for the determination of dioxins, dioxin-like PCBs and indicator-PCBs to ensure their rapid and reliable quantification in several kinds of food and feedingstuffs. Ideally one method would fit for several matrices with highest quality standards and with the possibility of a cost/time-effective samplehandling. However, generally in case of the numerous different PCDD/Fs, dioxin-like PCBs and indicator-PCBs as well as the large concentration range to cover this is quite difficult to fulfill. The implementation of an automated sample-treatment flow process (''dioxin street''), which contains an accelerated solvent extraction (ASE), a Power-Prep workstation (Fluid Management Systems, FMS) for automated clean-up, a Syncore Polyvap (Buechi, Switzerland) for solvent evaporation and a HRGC/HRMS (VG AutoSpec) analysis as detection method for several kinds of different matrices is described here. The aim of the present study is to confirm the high quality, low limits of quantification (LOQ), low PCB background levels and reliability of the Power-Prep system in combination with ASE extraction for dioxins, dioxin-like PCBs and indicator-PCBs.

  4. Diet-induced obesity: dopamine transporter function, impulsivity and motivation.

    Science.gov (United States)

    Narayanaswami, V; Thompson, A C; Cassis, L A; Bardo, M T; Dwoskin, L P

    2013-08-01

    A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure. Striatal D2-receptor density was determined by in vitro kinetic analysis of [(3)H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [(3)H]dopamine uptake, methamphetamine-evoked [(3)H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively. Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [(3)H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO. Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that

  5. Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Ferrante, Maria C.; Amero, Paola; Santoro, Anna; Monnolo, Anna; Simeoli, Raffaele; Di Guida, Francesca; Mattace Raso, Giuseppina; Meli, Rosaria

    2014-01-01

    Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are highly lipophilic environmental contaminants that accumulate in lipid-rich tissues, such as adipose tissue. Here, we reported the effects induced by PCBs 101, 153 and 180, three of the six NDL-PCBs defined as indicators, on mature 3T3-L1 adipocytes. We observed an increase in lipid content, in leptin gene expression and a reduction of leptin receptor expression and signaling, when cells were exposed to PCBs, alone or in combination. These modifications were consistent with the occurrence of “leptin-resistance” in adipose tissue, a typical metabolic alteration related to obesity. Therefore, we investigated how PCBs affect the expression of pivotal proteins involved in the signaling of leptin receptor. We evaluated the PCB effect on the intracellular pathway JAK/STAT, determining the phosphorylation of STAT3, a downstream activator of the transcription of leptin gene targets, and the expression of SOCS3 and PTP1B, two important regulators of leptin resistance. In particular, PCBs 153 and 180 or all PCB combinations induced a significant reduction in pSTAT3/STAT3 ratio and an increase in PTP1B and SOCS3, evidencing an additive effect. The impairment of leptin signaling was associated with the reduction of AMPK/ACC pathway activation, leading to the increase in lipid content. These pollutants were also able to increase the transcription of inflammatory cytokines (IL-6 and TNFα). It is worthy to note that the PCB concentrations used are comparable to levels detectable in human adipose tissue. Our data strongly support the hypothesis that NDL-PCBs may interfere with the lipid metabolism contributing to the development of obesity and related diseases. - Highlights: • NDL-PCBs alter lipid content and metabolism in 3T3-L1 adipocytes. • Impairment of leptin signaling was induced by NDL-PCBs. • NDL-PCBs reduce AMPK and ACC activation. • NDL-PCBs induce the synthesis of pro-inflammatory cytokine by

  6. Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ferrante, Maria C. [Department of Veterinary Medicine and Animal Productions, Federico II University of Naples, Via Delpino 1, 80137 Naples (Italy); Amero, Paola; Santoro, Anna [Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples (Italy); Monnolo, Anna [Department of Veterinary Medicine and Animal Productions, Federico II University of Naples, Via Delpino 1, 80137 Naples (Italy); Simeoli, Raffaele; Di Guida, Francesca [Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples (Italy); Mattace Raso, Giuseppina, E-mail: mattace@unina.it [Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples (Italy); Meli, Rosaria, E-mail: meli@unina.it [Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples (Italy)

    2014-09-15

    Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are highly lipophilic environmental contaminants that accumulate in lipid-rich tissues, such as adipose tissue. Here, we reported the effects induced by PCBs 101, 153 and 180, three of the six NDL-PCBs defined as indicators, on mature 3T3-L1 adipocytes. We observed an increase in lipid content, in leptin gene expression and a reduction of leptin receptor expression and signaling, when cells were exposed to PCBs, alone or in combination. These modifications were consistent with the occurrence of “leptin-resistance” in adipose tissue, a typical metabolic alteration related to obesity. Therefore, we investigated how PCBs affect the expression of pivotal proteins involved in the signaling of leptin receptor. We evaluated the PCB effect on the intracellular pathway JAK/STAT, determining the phosphorylation of STAT3, a downstream activator of the transcription of leptin gene targets, and the expression of SOCS3 and PTP1B, two important regulators of leptin resistance. In particular, PCBs 153 and 180 or all PCB combinations induced a significant reduction in pSTAT3/STAT3 ratio and an increase in PTP1B and SOCS3, evidencing an additive effect. The impairment of leptin signaling was associated with the reduction of AMPK/ACC pathway activation, leading to the increase in lipid content. These pollutants were also able to increase the transcription of inflammatory cytokines (IL-6 and TNFα). It is worthy to note that the PCB concentrations used are comparable to levels detectable in human adipose tissue. Our data strongly support the hypothesis that NDL-PCBs may interfere with the lipid metabolism contributing to the development of obesity and related diseases. - Highlights: • NDL-PCBs alter lipid content and metabolism in 3T3-L1 adipocytes. • Impairment of leptin signaling was induced by NDL-PCBs. • NDL-PCBs reduce AMPK and ACC activation. • NDL-PCBs induce the synthesis of pro-inflammatory cytokine by

  7. The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia.

    Science.gov (United States)

    Howes, Oliver D; McCutcheon, Robert; Owen, Michael J; Murray, Robin M

    2017-01-01

    The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia. Because it was initially based on indirect evidence and findings in patients with established schizophrenia, it was unclear what role dopamine played in the onset of the disorder. However, recent studies in people at risk of schizophrenia have found elevated striatal dopamine synthesis capacity and increased dopamine release to stress. Furthermore, striatal dopamine changes have been linked to altered cortical function during cognitive tasks, in line with preclinical evidence that a circuit involving cortical projections to the striatum and midbrain may underlie the striatal dopamine changes. Other studies have shown that a number of environmental risk factors for schizophrenia, such as social isolation and childhood trauma, also affect presynaptic dopaminergic function. Advances in preclinical work and genetics have begun to unravel the molecular architecture linking dopamine, psychosis, and psychosocial stress. Included among the many genes associated with risk of schizophrenia are the gene encoding the dopamine D 2 receptor and those involved in the upstream regulation of dopaminergic synthesis, through glutamatergic and gamma-aminobutyric acidergic pathways. A number of these pathways are also linked to the stress response. We review these new lines of evidence and present a model of how genes and environmental factors may sensitize the dopamine system so that it is vulnerable to acute stress, leading to progressive dysregulation and the onset of psychosis. Finally, we consider the implications for rational drug development, in particular regionally selective dopaminergic modulation, and the potential of genetic factors to stratify patients. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Does activation of midbrain dopamine neurons promote or reduce feeding?

    NARCIS (Netherlands)

    Boekhoudt, L.; Roelofs, T. J.M.; de Jong, J. W.; de Leeuw, A. E.; Luijendijk, M. C.M.; Wolterink-Donselaar, I. G.; van der Plasse, G.; Adan, R. A.H.

    Background:Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced

  9. Does activation of midbrain dopamine neurons promote or reduce feeding?

    NARCIS (Netherlands)

    Boekhoudt, L.; Roelofs, T. J. M.; de Jong, J. W.; de Leeuw, A. E.; Luijendijk, M. C. M.; Wolterink-Donselaar, I. G.; van der Plasse, G.; Adan, R. A. H.

    2017-01-01

    BACKGROUND: Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced

  10. The role of genes, stress and dopamine in the development of schizophrenia

    Science.gov (United States)

    Howes, Oliver D; McCutcheon, Robert; Owen, Michael J; Murray, Robin

    2017-01-01

    The dopamine hypothesis is the longest standing pathoaetiological theory of schizophrenia. As it was initially based on indirect evidence and findings in patients with established schizophrenia it was unclear what role dopamine played in the onset of the disorder. However, recent studies in people at risk of schizophrenia have found elevated striatal dopamine synthesis capacity, and increased dopamine release to stress. Furthermore, striatal dopamine changes have been linked to altered cortical function during cognitive tasks, in-line with preclinical evidence that a circuit involving cortical projections to the striatum and midbrain may underlie the striatal dopamine changes. Other studies have shown that a number of environmental risk factors for schizophrenia, such as social isolation and childhood trauma, also impact on presynaptic dopaminergic function. Advances in preclinical work and genetics have begun to unravel the molecular architecture linking dopamine, psychosis and psychosocial stress. Included among the many genes associated with risk of schizophrenia, are the gene encoding the DRD2 receptor and those involved in the up-stream regulation of dopaminergic synthesis, through glutamatergic and gamma-aminobutyric acid (GABA)-ergic pathways. A number of these pathways are also linked to the stress response. We review these new lines of evidence and present a model of how genes and environmental factors may sensitise the dopamine system so that it is vulnerable to acute stress, leading to progressive dysregulation and the onset of psychosis. Finally, we consider the implications for rational drug development, in particular regionally selective dopaminergic modulation, and the potential of genetic factors to stratify patients. PMID:27720198

  11. PCB's take a stroll Los PCBs salen de paseo

    OpenAIRE

    N. Olea Serrano; M. J. Begoña Olmos Ruiz; M. López Espinosa; M. Castillo Rodríguez

    2002-01-01

    Human exposure to bioaccumulable organochlorine compounds is a reality, not only because of the known presence in tissues of the residue of historic contaminants such as DDT and other pesticides, but also because of the risk of current exposure to compounds still in use, such as lindane, endosulphan and polychlorinated biphenyls or PCBs, among others. The case of the PCBs is of particular importance. Although their production was prohibited due to their hazardous nature, persistence and envir...

  12. Direct and indirect atmospheric deposition of PCBs to the Delaware River watershed.

    Science.gov (United States)

    Totten, Lisa A; Panangadan, Maya; Eisenreich, Steven J; Cavallo, Gregory J; Fikslin, Thomas J

    2006-04-01

    Atmospheric deposition can be an important source of PCBs to aquatic ecosystems. To develop the total maximum daily load (TMDL) for polychlorinated biphenyls (PCBs) for the tidal Delaware River (water-quality Zones 2-5), estimates of the loading of PCBs to the river from atmospheric deposition were generated from seven air-monitoring sites along the river. This paper presents the atmospheric PCB data from these sites, estimates direct atmospheric deposition fluxes, and assesses the importance of atmospheric deposition relative to other sources of PCBs to the river. Also, the relationship between indirect atmospheric deposition and PCB loads from minor tributaries to the Delaware River is discussed. Data from these sites revealed high atmospheric PCB concentrations in the Philadelphia/Camden urban area and lower regional background concentrations in the more remote areas. Wet, dry particle, and gaseous absorption deposition are estimated to contribute about 0.6, 1.8, and 6.5 kg year-(-1) sigmaPCBs to the River, respectively, exceeding the TMDL of 0.139 kg year(-1) by more than an order of magnitude. Penta-PCB watershed fluxes were obtained by dividing the tributary loads by the watershed area. The lowest of these watershed fluxes are less than approximately 1 ng m(-2) day(-1) for penta-PCB and probably indicates pristine watersheds in which PCB loads are dominated by atmospheric deposition. In these watersheds, the pass-through efficiency of PCBs is estimated to be on the order of 1%.

  13. A dopamine receptor d2-type agonist attenuates the ability of stress to alter sleep in mice.

    Science.gov (United States)

    Jefferson, F; Ehlen, J C; Williams, N S; Montemarano, J J; Paul, K N

    2014-11-01

    Although sleep disruptions that accompany stress reduce quality of life and deteriorate health, the mechanisms through which stress alters sleep remain obscure. Psychological stress can alter sleep in a variety of ways, but it has been shown to be particularly influential on rapid eye movement (REM) sleep. Prolactin (PRL), a sexually dimorphic, stress-sensitive hormone whose basal levels are higher in females, has somnogenic effects on REM sleep. In the current study, we examined the relationship between PRL secretion and REM sleep after restraint stress to determine whether: 1) the ability of stress to increase REM sleep is PRL-dependent, and 2) fluctuating PRL levels underlie sex differences in sleep responses to stress. Because dopamine D2 receptors in the pituitary gland are the primary regulator of PRL secretion, D2 receptor agonist, 1-[(6-allylergolin-8β-yl)-carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea (cabergoline), was used to attenuate PRL levels in mice before 1 hour of restraint stress. Mice were implanted with electroencephalographic/electromyographic recording electrodes and received an ip injection of either 0.3-mg/kg cabergoline or vehicle before a control procedure of 1 hour of sleep deprivation by gentle handling during the light phase. Six days after the control procedure, mice received cabergoline or vehicle 15 minutes before 1 hour of restraint stress. Cabergoline blocked the ability of restraint stress to increase REM sleep amount in males but did not alter REM sleep amount after stress in females even though it reduced basal REM sleep amount in female controls. These data provide evidence that the ability for restraint stress to increase REM sleep is dependent on PRL and that sex differences in REM sleep amount may be driven by PRL.

  14. Motor Function and Dopamine Release Measurements in Transgenic Huntington’s Disease Model Rats

    Science.gov (United States)

    Ortiz, Andrea N.; Osterhaus, Gregory L.; Lauderdale, Kelli; Mahoney, Luke; Fowler, Stephen C.; von Hörsten, Stephan; Riess, Olaf; Johnson, Michael A.

    2013-01-01

    Huntington’s disease (HD) is a fatal, genetic, neurodegenerative disorder characterized by deficits in motor and cognitive function. Here, we have quantitatively characterized motor deficiencies and dopamine release dynamics in transgenic HD model rats. Behavioral analyses were conducted using a newly-developed force-sensing runway and a previously-developed force-plate actometer. Gait disturbances were readily observed in transgenic HD rats at 12 to 15 months of age. Additionally, dopamine system challenge by ip injection of amphetamine also revealed that these rats were resistant to the expression of focused stereotypy compared to wild-type controls. Moreover, dopamine release, evoked by the application of single and multiple electrical stimulus pulses applied at different frequencies, and measured using fast-scan cyclic voltammetry at carbon-fiber microelectrodes, was diminished in transgenic HD rats compared to age-matched wild-type control rats. Collectively, these results underscore the potential contribution of dopamine release alterations to the expression of motor impairments in transgenic HD rats. PMID:22418060

  15. Serotonin 2B Receptors in Mesoaccumbens Dopamine Pathway Regulate Cocaine Responses.

    Science.gov (United States)

    Doly, Stéphane; Quentin, Emily; Eddine, Raphaël; Tolu, Stefania; Fernandez, Sebastian P; Bertran-Gonzalez, Jesus; Valjent, Emmanuel; Belmer, Arnauld; Viñals, Xavier; Callebert, Jacques; Faure, Philippe; Meye, Frank J; Hervé, Denis; Robledo, Patricia; Mameli, Manuel; Launay, Jean-Marie; Maldonado, Rafael; Maroteaux, Luc

    2017-10-25

    Addiction is a maladaptive pattern of behavior following repeated use of reinforcing drugs in predisposed individuals, leading to lifelong changes. Common among these changes are alterations of neurons releasing dopamine in the ventral and dorsal territories of the striatum. The serotonin 5-HT 2B receptor has been involved in various behaviors, including impulsivity, response to antidepressants, and response to psychostimulants, pointing toward putative interactions with the dopamine system. Despite these findings, it remains unknown whether 5-HT 2B receptors directly modulate dopaminergic activity and the possible mechanisms involved. To answer these questions, we investigated the contribution of 5-HT 2B receptors to cocaine-dependent behavioral responses. Male mice permanently lacking 5-HT 2B receptors, even restricted to dopamine neurons, developed heightened cocaine-induced locomotor responses. Retrograde tracing combined with single-cell mRNA amplification indicated that 5-HT 2B receptors are expressed by mesolimbic dopamine neurons. In vivo and ex vivo electrophysiological recordings showed that 5-HT 2B -receptor inactivation in dopamine neurons affects their neuronal activity and increases AMPA-mediated over NMDA-mediated excitatory synaptic currents. These changes are associated with lower ventral striatum dopamine activity and blunted cocaine self-administration. These data identify the 5-HT 2B receptor as a pharmacological intermediate and provide mechanistic insight into attenuated dopamine tone following exposure to drugs of abuse. SIGNIFICANCE STATEMENT Here we report that mice lacking 5-HT 2B receptors totally or exclusively in dopamine neurons exhibit heightened cocaine-induced locomotor responses. Despite the sensitized state of these mice, we found that associated changes include lower ventral striatum dopamine activity and lower cocaine operant self-administration. We described the selective expression of 5-HT 2B receptors in a subpopulation of

  16. Distinct Roles of Opioid and Dopamine Systems in Lateral Hypothalamic Intracranial Self-Stimulation.

    Science.gov (United States)

    Ide, Soichiro; Takahashi, Takehiro; Takamatsu, Yukio; Uhl, George R; Niki, Hiroaki; Sora, Ichiro; Ikeda, Kazutaka

    2017-05-01

    Opioid and dopamine systems play crucial roles in reward. Similarities and differences in the neural mechanisms of reward that are mediated by these 2 systems have remained largely unknown. Thus, in the present study, we investigated the differences in reward function in both µ-opioid receptor knockout mice and dopamine transporter knockout mice, important molecules in the opioid and dopamine systems. Mice were implanted with electrodes into the right lateral hypothalamus (l hour). Mice were then trained to put their muzzle into the hole in the head-dipping chamber for intracranial electrical stimulation, and the influences of gene knockout were assessed. Significant differences are observed between opioid and dopamine systems in reward function. µ-Opioid receptor knockout mice exhibited enhanced intracranial electrical stimulation, which induced dopamine release. They also exhibited greater motility under conditions of "despair" in both the tail suspension test and water wheel test. In contrast, dopamine transporter knockout mice maintained intracranial electrical stimulation responding even when more active efforts were required to obtain the reward. The absence of µ-opioid receptor or dopamine transporter did not lead to the absence of intracranial electrical stimulation responsiveness but rather differentially altered it. The present results in µ-opioid receptor knockout mice are consistent with the suppressive involvement of µ-opioid receptors in both positive incentive motivation associated with intracranial electrical stimulation and negative incentive motivation associated with depressive states. In contrast, the results in dopamine transporter knockout mice are consistent with the involvement of dopamine transporters in positive incentive motivation, especially its persistence. Differences in intracranial electrical stimulation in µ-opioid receptor and dopamine transporter knockout mice underscore the multidimensional nature of reward. © The Author

  17. The geography of mercury and PCBs in North Carolina’s local seafood

    International Nuclear Information System (INIS)

    Freitag, Amy; Sohn, Nari; Hooper, Mark; Rittschof, Dan

    2012-01-01

    Mercury and PCBs are used by non-governmental organizations and federal agencies to inform seafood safety recommendations. Pollution dynamics suggest recommendations on the national scale may be too large to be accurate. We tested softshell and hardshell blue crab, white and pink shrimp, oysters, clams, spot, and mullet from fishers in each of the three North Carolina fishery districts. We measured mercury using EPA method 7473 and PCBs using a commercially available ELISA kit. Over 97% of samples were below the Environmental Protection Agency levels of concern for both mercury and PCBs. Mercury and PCBs have different spatial dynamics, but both differ significantly by water body, suggesting that seafood safety recommendations should occur by water body instead of at the national scale. This finding supports previous research suggesting that differences in water chemistry, terrestrial influence, and flushing time in a particular water body control the contaminant load in locally resident species.

  18. Chlorinated hydrocarbons and PCBs in field soils, sediments and sewage sludges

    International Nuclear Information System (INIS)

    Schaaf, H.

    1992-01-01

    As requested by the Ministry of Agriculture of the FRG, the 'Verband Deutscher Landwirtschaftlicher Untersuchungs- und Forschungsanstalten (VDLUFA)' built up a data collection over chlorinated hydrocarbons and PCBs in field soils, sediments, sewage sludges. Nearly 70.000 samples were collected and statistically evaluated. The results of these investigations will be described. The major constituents of the chlorinated hydrocarbons generally were Lindane, DDT(total) and HCB. In sewage sludges PCBs could be detected in nearly every sample. The contents of PCBs in field soils are smaller than in sewage sludges. Rather 'high contents', greater than 100-200 μg/kg d.m./organic pollutants, were detected only in 2% of the samples. 7 refs., 5 figs., 2 tabs

  19. Assessment of Polychlorinated Biphenyls (PCBs) in Water ...

    African Journals Online (AJOL)

    PROF HORSFALL

    Attribution License (CCL), which permits unrestricted use, distribution, and reproduction in any medium, provided the original ... expectancy of electrical transformers that contain PCBs ... Convention for Protection of the Marine Environment of.

  20. Neurodevelopmental toxicity of prenatal polychlorinated biphenyls (PCBs by chemical structure and activity: a birth cohort study

    Directory of Open Access Journals (Sweden)

    Park Hye-Youn

    2010-08-01

    Full Text Available Abstract Background Polychlorinated biphenyls (PCBs are ubiquitous environmental toxins. Although there is growing evidence to support an association between PCBs and deficits of neurodevelopment, the specific mechanisms are not well understood. The potentially different roles of specific PCB groups defined by chemical structures or hormonal activities e.g., dioxin-like, non-dioxin like, or anti-estrogenic PCBs, remain unclear. Our objective was to examine the association between prenatal exposure to defined subsets of PCBs and neurodevelopment in a cohort of infants in eastern Slovakia enrolled at birth in 2002-2004. Methods Maternal and cord serum samples were collected at delivery, and analyzed for PCBs using high-resolution gas chromatography. The Bayley Scales of Infant Development -II (BSID were administered at 16 months of age to over 750 children who also had prenatal PCB measurements. Results Based on final multivariate-adjusted linear regression model, maternal mono-ortho-substituted PCBs were significantly associated with lower scores on both the psychomotor (PDI and mental development indices (MDI. Also a significant association between cord mono-ortho-substituted PCBs and reduced PDI was observed, but the association with MDI was marginal (p = 0.05. Anti-estrogenic and di-ortho-substituted PCBs did not show any statistically significant association with cognitive scores, but a suggestive association between di-ortho-substituted PCBs measured in cord serum and poorer PDI was observed. Conclusion Children with higher prenatal mono-ortho-substituted PCB exposures performed more poorly on the Bayley Scales. Evidence from this and other studies suggests that prenatal dioxin-like PCB exposure, including mono-ortho congeners, may interfere with brain development in utero. Non-dioxin-like di-ortho-substituted PCBs require further investigation.

  1. Toxicological effects of polychlorinated biphenyls (PCBs) on freshwater turtles in the United States.

    Science.gov (United States)

    Ming-Ch'eng Adams, Clare Isabel; Baker, Joel E; Kjellerup, Birthe V

    2016-07-01

    Prediction of vertebrate health effects originating from persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) has remained a challenge for decades thus making the identification of bioindicators difficult. POPs are predominantly present in soil and sediment, where they adhere to particles due to their hydrophobic characteristics. Animals inhabiting soil and sediment can be exposed to PCBs via dermal exposure while others may obtain PCBs through contaminated trophic interaction. Freshwater turtles can serve as bioindicators due to their strong site fidelity, longevity and varied diet. Previous research observed the health effects of PCBs on turtles such as decreased bone mass, changed sexual development and decreased immune responses through studying both contaminated sites along with laboratory experimentation. Higher deformity rates in juveniles, increased mortality and slower growth have also been observed. Toxicological effects of PCBs vary between species of freshwater turtles and depend on the concertation and configuration of PCB congeners. Evaluation of ecotoxicological effects of PCBs in non-endangered turtles could provide important knowledge about the health effects of endangered turtle species thus inform the design of remediation strategies. In this review, the PCB presence in freshwater turtle habitats and the ecotoxicological effects were investigated with the aim of utilizing the health status to identify areas of focus for freshwater turtle conservation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The associations between the environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk and progression

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Polychlorinated biphenyls(PCBs) are chlorinated biphenyl compounds with wide applications in the industry.In spite of a ban on their production in the late 1970s,PCBs,as a group of POPs,are still persistent and widely spread in the environment,posing potential threats to human health.The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo,animal and epidemiologic studies.Initial investigations indicated higher levels of PCBs in mammary tissues or sera corresponded to the occurrence of breast cancer,but later studies showed no positive association between PCB exposure and breast cancer development.More recent data suggested that the CYP1A1 m2 polymorphisms might add increased risk to the etiology of breast cancer in women with environmental exposure to PCBs.PCBs are implicated in advancing breast cancer progression,and our unpublished data reveals that PCBs activate the ROCK signaling to enhance breast cancer metastasis.Therefore,the correlation between PCB exposure and breast cancer risk warrants further careful investigations.

  3. Fetal exposure to PCBs and their hydroxylated metabolites in a Dutch cohort

    NARCIS (Netherlands)

    Soechitram, S.D.; Athanasiadou, M.; Hovander, L.; Bergman, A.; Sauer, P. J. J.

    2004-01-01

    Polychlorinated biphenyls (PCBs) are still the most abundant pollutants in wildlife and humans. Hydroxylated PCB metabolites (OH-PCBs) are known to be formed in humans and wildlife. Studies in animals show that these metabolites cause endocrine-related toxicity. The health effects in humans have not

  4. Decontamination of PCBs-containing soil using subcritical water extraction process.

    Science.gov (United States)

    Islam, Mohammad Nazrul; Park, Jeong-Hun; Shin, Moon-Su; Park, Ha-Seung

    2014-08-01

    Polychlorinated biphenyls (PCBs) are one of the excision compounds listed at the Stockholm convention in 2001. Although their use has been heavily restricted, PCBs can be found in some specific site-contaminated soils. Either removal or destruction is required prior to disposal. The subcritical water extraction (SCWE) of organic hazardous compounds from contaminated soils is a promising technique for hazardous waste contaminated-site cleanup. In this study, the removal of PCBs by the SCWE process was investigated. The effects of temperature and treatment time on removal efficiency have been determined. In the SCWE experiments, a removal percentage of 99.7% was obtained after 1h of treatment at 250°C. The mass removal efficiency of low-chlorinated species was higher than high-chlorinated congeners at lower temperatures, but it was oppositely observed at higher temperatures because the lower chlorinated congeners are formed by dechlorination of higher chlorinated congeners. Gas chromatography/mass spectrometry analysis confirmed that the PCBs underwent partial degradation. Several degradation products including mono- and di-chlorinated biphenyls, oxygen-containing aromatic compounds, and small-size hydrocarbons were identified in the effluent water, which were not initially present in the contaminated soil. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Dopamine-induced apoptosis in human neuronal cells: inhibition by nucleic acides antisense to the dopamine transporter

    International Nuclear Information System (INIS)

    Porat, S.; Gabbay, M.; Tauber, M.; Ratovitski, T.; Blinder, E.; Simantov, R.

    1996-01-01

    Human neuroblastoma NMB cells take up [ 3 H]dopamine in a selective manner indicating that dopamine transporters are responsible for this uptake. These cells were therefore used as a model to study dopamine neurotoxicity, and to elucidate the role of dopamine transporters in controlling cell death. Treatment with 0.05-0.4 mM dopamine changed cells' morphology within 4 h, accompanied by retraction of processes, shrinkage, apoptosis-like atrophy, accumulation of apoptotic particles, DNA fragmentation and cell death. Cycloheximide inhibited dopamine's effect, suggesting that induction of apoptosis by dopamine was dependent upon protein synthesis. Dopamine cytotoxicity, monitored morphologically by flow cytometric analysis, and by lactate dehydrogenase released, was blocked by cocaine but not by the noradrenaline and serotonin uptake blockers desimipramine and imipramine, respectively. Attempting to inhibit dopamine transport and toxicity in a drug-free and highly selective way, three 18-mer dopamine transporter antisense phosphorothioate oligonucleotides (numbers 1, 2 and 3) and a new plasmid vector expressing the entire rat dopamine transporter complementary DNA in the antisense orientation were prepared and tested. Antisense phosphorothioate oligonucleotide 3 inhibited [ 3 H]dopamine uptake in a time- and dose-dependent manner. Likewise, transient transfection of NMB cells with the plasmid expressing dopamine transporter complementary DNA in the antisense orientation partially blocked [ 3 H]dopamine uptake. Antisense phosphorothioate oligonucleotide 3 also decreased, dose-dependently, the toxic effect of dopamine and 6-hydroxydopamine. Western blot analysis with newly prepared anti-human dopamine transporter antibodies showed that antisense phosphorothioate oligonucleotide 3 decreased the transporter protein level. These studies contribute to better understand the mechanism of dopamine-induced apoptosis and neurotoxicity. (Copyright (c) 1996 Elsevier Science B

  6. Co-ordinate transcriptional regulation of dopamine synthesis genes by alpha-synuclein in human neuroblastoma cell lines.

    Science.gov (United States)

    Baptista, Melisa J; O'Farrell, Casey; Daya, Sneha; Ahmad, Rili; Miller, David W; Hardy, John; Farrer, Matthew J; Cookson, Mark R

    2003-05-01

    Abnormal accumulation of alpha-synuclein in Lewy bodies is a neuropathological hallmark of both sporadic and familial Parkinson's disease (PD). Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic cell death occurs remains unknown. We investigated transcriptional changes in neuroblastoma cell lines transfected with either normal or mutant (A30P or A53T) alpha-synuclein using microarrays, with confirmation of selected genes by quantitative RT-PCR. Gene products whose expression was found to be significantly altered included members of diverse functional groups such as stress response, transcription regulators, apoptosis-inducing molecules, transcription factors and membrane-bound proteins. We also found evidence of altered expression of dihydropteridine reductase, which indirectly regulates the synthesis of dopamine. Because of the importance of dopamine in PD, we investigated the expression of all the known genes in dopamine synthesis. We found co-ordinated downregulation of mRNA for GTP cyclohydrolase, sepiapterin reductase (SR), tyrosine hydroxylase (TH) and aromatic acid decarboxylase by wild-type but not mutant alpha-synuclein. These were confirmed at the protein level for SR and TH. Reduced expression of the orphan nuclear receptor Nurr1 was also noted, suggesting that the co-ordinate regulation of dopamine synthesis is regulated through this transcription factor.

  7. Dopamine Manipulation Affects Response Vigor Independently of Opportunity Cost.

    Science.gov (United States)

    Zénon, Alexandre; Devesse, Sophie; Olivier, Etienne

    2016-09-14

    Dopamine is known to be involved in regulating effort investment in relation to reward, and the disruption of this mechanism is thought to be central in some pathological situations such as Parkinson's disease, addiction, and depression. According to an influential model, dopamine plays this role by encoding the opportunity cost, i.e., the average value of forfeited actions, which is an important parameter to take into account when making decisions about which action to undertake and how fast to execute it. We tested this hypothesis by asking healthy human participants to perform two effort-based decision-making tasks, following either placebo or levodopa intake in a double blind within-subject protocol. In the effort-constrained task, there was a trade-off between the amount of force exerted and the time spent in executing the task, such that investing more effort decreased the opportunity cost. In the time-constrained task, the effort duration was constant, but exerting more force allowed the subject to earn more substantial reward instead of saving time. Contrary to the model predictions, we found that levodopa caused an increase in the force exerted only in the time-constrained task, in which there was no trade-off between effort and opportunity cost. In addition, a computational model showed that dopamine manipulation left the opportunity cost factor unaffected but altered the ratio between the effort cost and reinforcement value. These findings suggest that dopamine does not represent the opportunity cost but rather modulates how much effort a given reward is worth. Dopamine has been proposed in a prevalent theory to signal the average reward rate, used to estimate the cost of investing time in an action, also referred to as opportunity cost. We contrasted the effect of dopamine manipulation in healthy participants in two tasks, in which increasing response vigor (i.e., the amount of effort invested in an action) allowed either to save time or to earn more

  8. Decomposition of PCBs in transformer oil using an electron beam accelerator

    International Nuclear Information System (INIS)

    Jung, In-Ha; Lee, Myun-Joo; Mah, Yoon-Jung

    2012-01-01

    Decomposition of PCBs in commercially used transformer oil used for more than 30 years has been carried out at normal temperature and pressure without any additives using an electron beam accelerator. The experiments were carried out in two ways: batch and continuous pilot plant with 1.5 MeV of energy, a 50 mA current, and 75 kW of power in a commercial scale accelerator. The electron beam irradiation seemed to transform large molecular weight compounds into lower ones, but the impact was considered too small on the physical properties of oil. Residual concentrations of PCBs after irradiation depend on the absorption dose of the electron beam energy, but aliphatic chloride compounds were produced at higher doses of irradiation. As the results from FT-NMR, chloride ions decomposed from the PCBs are likely to react with aliphatic hydro carbon compounds rather than existing as free radical ions in the transformer oil. Since this is a dry process, treated oil can be used as cutting oil or machine oil for heavy equipment without any additional treatments. - Highlights: ► We developed a novel technology of decomposing PCBs in transformer oil using an electron beam. ► Distinct feature is accomplishing at ambient temperature and pressure without any additives. ► Residual PCBs were depended on absorption dose, but aliphatic chlorides were produced at higher dose. ► Treated oil can be reused as heating oil with chlorine removal technology developed here.

  9. Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease.

    Science.gov (United States)

    Zucca, Fabio A; Segura-Aguilar, Juan; Ferrari, Emanuele; Muñoz, Patricia; Paris, Irmgard; Sulzer, David; Sarna, Tadeusz; Casella, Luigi; Zecca, Luigi

    2017-08-01

    There are several interrelated mechanisms involving iron, dopamine, and neuromelanin in neurons. Neuromelanin accumulates during aging and is the catecholamine-derived pigment of the dopamine neurons of the substantia nigra and norepinephrine neurons of the locus coeruleus, the two neuronal populations most targeted in Parkinson's disease. Many cellular redox reactions rely on iron, however an altered distribution of reactive iron is cytotoxic. In fact, increased levels of iron in the brain of Parkinson's disease patients are present. Dopamine accumulation can induce neuronal death; however, excess dopamine can be removed by converting it into a stable compound like neuromelanin, and this process rescues the cell. Interestingly, the main iron compound in dopamine and norepinephrine neurons is the neuromelanin-iron complex, since neuromelanin is an effective metal chelator. Neuromelanin serves to trap iron and provide neuronal protection from oxidative stress. This equilibrium between iron, dopamine, and neuromelanin is crucial for cell homeostasis and in some cellular circumstances can be disrupted. Indeed, when neuromelanin-containing organelles accumulate high load of toxins and iron during aging a neurodegenerative process can be triggered. In addition, neuromelanin released by degenerating neurons activates microglia and the latter cause neurons death with further release of neuromelanin, then starting a self-propelling mechanism of neuroinflammation and neurodegeneration. Considering the above issues, age-related accumulation of neuromelanin in dopamine neurons shows an interesting link between aging and neurodegeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Blink Rate in Boys with Fragile X Syndrome: Preliminary Evidence for Altered Dopamine Function

    Science.gov (United States)

    Roberts, J. E.; Symons, F. J.; Johnson, A.-M.; Hatton, D. D.; Boccia, M. L.

    2005-01-01

    Background: Dopamine, a neurotransmitter involved in motor and cognitive functioning, can be non-invasively measured via observation of spontaneous blink rates. Blink rates have been studied in a number of clinical conditions including schizophrenia, autism, Parkinsons, and attention deficit/hyperactivity disorder with results implicating either…

  11. Bidirectional modulation of goal-directed actions by prefrontal cortical dopamine.

    Science.gov (United States)

    Hitchcott, Paul K; Quinn, Jennifer J; Taylor, Jane R

    2007-12-01

    Instrumental actions are a vital cognitive asset that endows an organism with sensitivity to the consequences of its behavior. Response-outcome feedback allows responding to be shaped in order to maximize beneficial, and minimize detrimental, outcomes. Lesions of the medial prefrontal cortex (mPFC) result in behavior that is insensitive to changes in outcome value in animals and compulsive behavior in several human psychopathologies. Such insensitivity to changes in outcome value is a defining characteristic of instrumental habits: responses that are controlled by antecedent stimuli rather than goal expectancy. Little is known regarding the neurochemical substrates mediating this sensitivity. The present experiments used sensitivity to posttraining outcome devaluation to index the action-habit status of instrumental responding. Infusions of dopamine into the ventral mPFC (vmPFC), but not dorsal mPFC, restored outcome sensitivity bidirectionally-decreasing responding following outcome devaluation and increasing responding when the outcome was not devalued. This bidirectionality makes the possibility that these infusions nonspecifically dysregulated vmPFC dopamine transmission unlikely. VmPFC dopamine promoted instrumental responding appropriate to outcome value. Reinforcer consumption data indicated that this was not a consequence of altered sensitivity to the reinforcer itself. We suggest that vmPFC dopamine reengages attentional processes underlying goal-directed behavior.

  12. Presence of polychlorinated biphenyls (PCBs) in bottled drinking water in Mexico City.

    Science.gov (United States)

    Salinas, Rutilio Ortiz; Bermudez, Beatriz Schettino; Tolentino, Rey Gutiérrez; Gonzalez, Gilberto Díaz; Vega y León, Salvador

    2010-10-01

    This paper describes the concentrations of seven polychlorinated biphenyls (PCBs) in bottled drinking water samples that were collected over 1 year from Mexico City in two sizes (1.5 and 19 L), using gas chromatography with an electron capture detector. PCBs 28 (0.018-0.042 μg/L), 52 (0.006-0.015 μg/L) and 101 (0.001-0.039 μg/L) were the most commonly found and were present in the majority of the samples. However, total concentrations of PCBs in bottled drinking water (0.035-0.039 μg/L) were below the maximum permissible level of 0.50 μg/L stated in Mexican regulations and probably do not represent a hazard to human health. PCBs were detectable in all samples and we recommend a monitoring program be established to better understand the quality of drinking bottled water over time; this may help in producing solutions for reducing the presence of organic contaminants.

  13. Thyroid hormone-like and estrogenic activity of hydroxylated PCBs in cell culture

    International Nuclear Information System (INIS)

    Kitamura, Shigeyuki; Jinno, Norimasa; Suzuki, Tomoharu; Sugihara, Kazumi; Ohta, Shigeru; Kuroki, Hiroaki; Fujimoto, Nariaki

    2005-01-01

    The thyroid hormone-disrupting activity of hydroxylated PCBs was examined. 4-Hydroxy-2,2',3,4',5,5'-hexachlorobiphenyl (4-OH-2,2',3,4',5,5'-HxCB), 4-hydroxy-3,3',4',5-tetrachlorobiphenyl (4-OH-3,3',4',5-TCB) and 4,4'-dihydroxy-3,3',5,5'-tetrachlorobiphenyl (4,4'-diOH-3,3',5,5'-TCB), which have been detected as metabolites of PCBs in animals and humans, and six other 4-hydroxylated PCBs markedly inhibited the binding of triiodothyronine (1 x 10 -10 M) to thyroid hormone receptor (TR) in the concentration range of 1 x 10 -6 to 1 x 10 -4 M. However, 4-hydroxy-2',4',6'-trichlorobiphenyl (4-OH-2',4',6'-TCB), 3-hydroxy-2,2',5,5'-tetrachlorobiphenyl, 4-hydroxy-2,2',5,5'-tetrachlorobiphenyl, 4-hydroxy-2,3,3',4'-tetrachlorobiphenyl, 2,3',5,5'-tetrachlorobiphenyl and 2,3',4',5,5'-pentachlorodiphenyl did not show affinity for TR. The thyroid hormonal activity of PCBs was also examined using rat pituitary cell line GH3 cells, which grow and release growth hormone in a thyroid hormone-dependent manner. 4-OH-2,2',3,4',5,5'-HxCB, 4,4'-diOH-3,3',5,5'-TCB and 4-OH-3,3',4',5-TCB enhanced the proliferation of GH3 cells and stimulated their production of growth hormone in the concentration range of 1 x 10 -7 to 1 x 10 -4 M, while PCBs which had no affinity for thyroid hormone receptor were inactive. In contrast, only 4-OH-2',4',6'-TCB exhibited a significant estrogenic activity using estrogen-responsive reporter assay in MCF-7 cells. However, the 3,5-dichloro substitution of 4-hydroxylated PCBs markedly decreased the estrogenic activity. These results suggest that, at least for the 17 PCB congeners and hydroxylated metabolites tested, a 4-hydroxyl group in PCBs is essential for thyroid hormonal and estrogenic activities, and that 3,5-dichloro substitution favors thyroid hormonal activity, but not estrogenic activity

  14. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel

    2006-03-01

    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  15. The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

    Science.gov (United States)

    Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

    2014-07-01

    The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  16. Dopamine D(1) receptor-mediated control of striatal acetylcholine release by endogenous dopamine.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-10-27

    The role of dopamine D(1) and D(2) receptors in the control of acetylcholine release in the dorsal striatum by endogenous dopamine was investigated by monitoring with microdialysis the effect of the separate or combined administration of the dopamine D(1) receptor antagonist, SCH 39166 ¿(-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride¿ (50 microg/kg subcutaneous (s.c.)), of the dopamine D(2)/D(3) receptor agonist, quinpirole (trans-(-)-4aR, 4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3,4-g)-quinoline hydrochloride) (5 and 10 microg/kg s.c.), and of the D(3) receptor selective agonist, PD 128,907 [S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin -9-ol hydrochloride] (50 microg/kg s.c.), on in vivo dopamine and acetylcholine release. Microdialysis was performed with a Ringer containing low concentrations (0.01 microM) of the acetylcholinesterase inhibitor, neostigmine. Quinpirole (10 microg/kg s.c.) decreased striatal dopamine and acetylcholine release. Administration of PD 128,907 (50 microg/kg) decreased dopamine but failed to affect acetylcholine release. SCH 39166 (50 microg/kg s.c.) stimulated dopamine release and reduced acetylcholine release. Pretreatment with quinpirole reduced (5 microg/kg s.c.) or completely prevented (10 microg/kg s.c.) the stimulation of dopamine release elicited by SCH 39166 (50 microg/kg s.c.); on the other hand, pretreatment with quinpirole (5 and 10 microg/kg) potentiated the reduction of striatal acetylcholine release induced by SCH 39166 (50 microg/kg s.c.). Similarly, pretreatment with PD 128,907 (50 microg/kg) which prevented the increase of dopamine release induced by SCH 39166 (50 microg/kg), potentiated the reduction of striatal acetylcholine transmission elicited by SCH 39166. Thus, pretreatment with low doses of quinpirole or PD 128,907 influences in opposite manner the effect of SCH 39166 on striatal dopamine and

  17. Exposure assessment of dioxins and dioxin-like PCBs in pasteurised bovine milk using probabilistic modelling.

    Science.gov (United States)

    Adekunte, Adefunke O; Tiwari, Brijesh K; O'Donnell, Colm P

    2010-09-01

    Quantitative exposure assessment is a useful technique to investigate the risk from contaminants in the food chain. The objective of this study was to develop a probabilistic exposure assessment model for dioxins (PCDD/Fs) and dioxin-like PCBs (DL-PCBs) in pasteurised bovine milk. Mean dioxins and DL-PCBs (non-ortho and mono-ortho PCBs) concentrations (pg WHO-TEQ g(-1)) in bovine milk were estimated as 0.06 ± 0.07 pg WHO-TEQ g(-1) for dioxins and 0.08 ± 0.07 pg WHO-TEQ g(-1) for DL-PCBs using Monte Carlo simulation. The simulated model estimated mean exposure for dioxins was 0.19 ± 0.29 pg WHO-TEQ kg(-1)bw d(-1) and 0.14 ± 0.22 pg WHO-TEQ kg(-1) bw d(-1) and for DL-PCBs was 0.25 ± 0.30 pg WHO-TEQ kg(-1) bw d(-1) and 0.19 ± 0.22 pg WHO-TEQ kg(-1) bw d(-1) for men and women, respectively. This study showed that the mean dioxins and DL-PCBs exposure from consumption of pasteurised bovine milk is below the provisional maximum tolerable monthly intake of 70 pg TEQ kg(-1) bw month(-1) (equivalent of 2.3 pg TEQ kg(-1) bw d(-1)) recommended by the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (JECFA). Results from this study also showed that the estimated dioxins and DL-PCBs concentration in pasteurised bovine milk is comparable to those reported in previous studies. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

    Science.gov (United States)

    Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

    2017-11-01

    Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat

  19. Import, use, and emissions of PCBs in Switzerland from 1930 to 2100.

    Directory of Open Access Journals (Sweden)

    Juliane Glüge

    Full Text Available Polychlorinated biphenyls (PCBs are persistent organic compounds that are ubiquitously found in the environment. Their use and manufacture were restricted or banned in many countries in the 1970-1980s, however, they still persist in the antroposphere, the environment and in biota worldwide today. Conventions like the Convention on Long-range Transboundary Air Pollution encourage or bind the member parties to annually submit emission inventories of regulated air pollutants. Unfortunately, several member states have not yet reported PCB emissions. The identification and quantification of stocks and emissions sources is, however, an important precondition to handle and remove the remaining reservoirs of PCBs and, thus, to be able to reduce emissions and subsequently environmental exposure. Here, we estimate past, present, and future emissions of PCBs to air in Switzerland and provide emission factors for all relevant emission categories. Switzerland hereby represents a typical developed industrial country, and most of the assumptions and parameters presented here can be used to calculate PCB emission also for other countries. PCB emissions to air are calculated using a dynamic mass flow and emissions model for Switzerland, which is run for the years 1930-2100. The results point out the importance of the use of PCBs in open applications, which have largely been previously overlooked. Additionally, we show that PCBs will persist in applications during the coming decades with ongoing emissions. Especially the use of PCBs in open applications will cause Swiss emissions to remain above 100 kg PCB per year, even after the year 2030. Our developed model is available in Excel/VBA and can be downloaded with this article.

  20. Import, use, and emissions of PCBs in Switzerland from 1930 to 2100.

    Science.gov (United States)

    Glüge, Juliane; Steinlin, Christine; Schalles, Simone; Wegmann, Lukas; Tremp, Josef; Breivik, Knut; Hungerbühler, Konrad; Bogdal, Christian

    2017-01-01

    Polychlorinated biphenyls (PCBs) are persistent organic compounds that are ubiquitously found in the environment. Their use and manufacture were restricted or banned in many countries in the 1970-1980s, however, they still persist in the antroposphere, the environment and in biota worldwide today. Conventions like the Convention on Long-range Transboundary Air Pollution encourage or bind the member parties to annually submit emission inventories of regulated air pollutants. Unfortunately, several member states have not yet reported PCB emissions. The identification and quantification of stocks and emissions sources is, however, an important precondition to handle and remove the remaining reservoirs of PCBs and, thus, to be able to reduce emissions and subsequently environmental exposure. Here, we estimate past, present, and future emissions of PCBs to air in Switzerland and provide emission factors for all relevant emission categories. Switzerland hereby represents a typical developed industrial country, and most of the assumptions and parameters presented here can be used to calculate PCB emission also for other countries. PCB emissions to air are calculated using a dynamic mass flow and emissions model for Switzerland, which is run for the years 1930-2100. The results point out the importance of the use of PCBs in open applications, which have largely been previously overlooked. Additionally, we show that PCBs will persist in applications during the coming decades with ongoing emissions. Especially the use of PCBs in open applications will cause Swiss emissions to remain above 100 kg PCB per year, even after the year 2030. Our developed model is available in Excel/VBA and can be downloaded with this article.

  1. Transformation of chiral polychlorinated biphenyls (PCBs) in a stream food web

    Science.gov (United States)

    Dang, V.D.; Walters, D.M.; Lee, C.M.

    2010-01-01

    The enantiomeric composition of chiral PCB congeners was determined in Twelvemile Creek (Clemson, SC) to examine potential mechanisms of biotransformation in a stream food web. We measured enantiomeric fractions (EFs) of six PCB atropisomers (PCBs 84, 91, 95, 136, 149, and 174) in surface sediment, fine benthic organic matter (FBOM), coarse particulate organic matter (CPOM), periphyton, Asian clam, mayflies, yellowfin shiner, and semipermeable membrane devices (SPMDs) using gas chromatography (GC-ECD). Nonracemic EFs of PCBs 91, 95, 136, and 149 were measured in almost all samples. Enantiomeric compositions of PCBs 84 and 174 were infrequently detected with racemic EFs measured in samples except for a nonracemic EF of PCB 84 in clams. Nonracemic EFs of PCBs 91, 136, and 149 in SPMDs may be due to desorption of nonracemic residues from FBOM. EFs for some atropisomers were significantly different among FBOM, CPOM, and periphyton, suggesting that their microbial communities have different biotransformation processes. Nonracemic EFs in clams and fish suggest both in vivo biotransformation and uptake of nonracemic residues from their food sources. Longitudinal variability in EFs was generally low among congeners observed in matrices. ?? 2010 American Chemical Society.

  2. Learning from Dioxin & PCBs in meat - problems ahead?

    Science.gov (United States)

    Weber, R.

    2017-09-01

    Persistent organic pollutants (POPs) including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs; “Dioxins”), or polychlorinated biphenyls (PCBs) are widely recognized environmental and food contaminants. More than 90% of PCDD/Fs and PCB exposure of the average population stem from animal based food including meat. While average PCDD/F and PCB levels have decreased compared to levels 1980s, still contamination above regulatory limits are observed and a share of the population is above the tolerable daily intake recommended by the WHO. For PCBs the contamination of feed and food along the life cycle from production, use, recycling, end of life and related contaminated sites has been documented and can be seen as a model. Furthermore, it has been recently discovered that levels of PCBs in feed and soil below regulatory limits can result in meat contamination above EU regulatory limits. In particular, beef meat and chicken meat/eggs have been found very sensitive towards PCB contamination in the environment (soil and feed) but also in stables (paints and sealants). For PCDD/Fs, the major exposure pathways are feed, feed additives and contaminated sites. Chlorinated paraffins have substituted PCBs the last 40 years in open application and short chain chlorinated paraffins (SCCPs) were recently (05/2017) listed in the Stockholm Convention. Furthermore, brominated and fluorinated POPs have been listed in the Convention. All these POPs groups can accumulate in meat animals. For these new listed POPs no regulatory limits in food including meat has been established yet. Initial information on presence and risk of new listed POPs to food animals is compiled. A more systematic assessment of exposure and risks of POPs to food animals/meat is needed.

  3. Dopamine receptors in the Parkinsonian brain

    Energy Technology Data Exchange (ETDEWEB)

    Rinne, U K; Loennberg, P; Koskinen, V [Turku Univ. (Finland). Dept. of Neurology

    1981-01-01

    Striatal dopamine receptors were studied in 44 patients with Parkinson disease by the radioligand-binding technique using /sup 3/H-spiroperidol. The specific binding of /sup 3/H-spiroperidol was either significantly increased or reduced in the caudate nucleus and putamen of parkinsonian patients without levodopa therapy. Scatchard analysis showed that there were corresponding changes in the receptor number, but no significant changes in the mean dissociation constant. The increased binding of /sup 3/H-spiroperidol in the basal ganglia was also found in parkinsonian patients suffering from psychotic episodes and treated with neuroleptic drugs. Normal and low binding of /sup 3/H-spiroperidol was found in patients treated with levodopa. Clinically, the patient with low binding were more disabled and had lost the beneficial response to levodopa. Thus in Parkinson disease in some patients a denervation supersensitivity seemed to develop and in some others a loss of postsynaptic dopamine receptor sites in the neostriatium. The latter alteration may contribute to the decreased response of parkinsonian patients to chronic levodopa therapy.

  4. Dopamine receptors in the Parkinsonian brain

    International Nuclear Information System (INIS)

    Rinne, U.K.; Loennberg, P.; Koskinen, V.

    1981-01-01

    Striatal dopamine receptors were studied in 44 patients with Parkinson disease by the radioligand-binding technique using 3 H-spiroperidol. The specific binding of 3 H-spiroperidol was either significantly increased or reduced in the caudate nucleus and putamen of parkinsonian patients without levodopa therapy. Scatchard analysis showed that there were corresponding changes in the receptor number, but no significant changes in the mean dissociation constant. The increased binding of 3 H-spiroperidol in the basal ganglia was also found in parkinsonian patients suffering from psychotic episodes and treated with neuroleptic drugs. Normal and low binding of 3 H-spiroperidol was found in patients treated with levodopa. Clinically, the patient with low binding were more disabled and had lost the beneficial response to levodopa. Thus in Parkinson disease in some patients a denervation supersensitivity seemed to develop and in some others a loss of postsynaptic dopamine receptor sites in the neostriatium. The latter alteration may contribute to the decreased response of parkinsonian patients to chronic levodopa therapy. (author)

  5. Reducing the bioavailability of PCBs in soil to plant by biochars assessed with triolein-embedded cellulose acetate membrane technique

    International Nuclear Information System (INIS)

    Wang, Yu; Wang, Yu-Jun; Wang, Lei; Fang, Guo-Dong; Cang, Long; Herath, H.M.S.K.; Zhou, Dong-Mei

    2013-01-01

    Coupling with triolein-embedded cellulose acetate membrane (TECAM) technique, hydroxypropyl β-cyclodextrins (HPCD) extraction method, and the greenhouse pot experiments, the influences of biochars on polychlorinated biphenyls (PCBs) bioavailability in soil to plant (Brassica chinensis L. and Daucus carota) were investigated. Addition of 2% biochars to soils significantly reduced the uptake of PCBs in plant, especially for di-, tri- and tetra-chlorobiphenyls. PCBs concentrations in the roots of B. chinensis and D. carota were reduced for 61.5–93.7%, and 12.7–62.4%, respectively in the presence of biochars. The kinetic study showed that in the soils amended with/without biochars, PCBs concentrations accumulated in TECAM, as well as in the HPCD extraction solution, followed significant linear relationships with those in plant roots. Application of biochars to soil is a potentially promising method to reduce PCBs bioavailability whereas TECAM technique can be a useful tool to predict the bioavailability of PCBs in soil. -- Highlights: ► Application of biochars significantly reduced the uptake of PCBs in plant. ► TECAM was a new and effective method to predict the PCBs bioavailability in soil. ► PCBs accumulated in TECAM followed significant linear relationships with plant. ► PCBs in TECAM were more similar with the plant uptake than HPCD solution. -- The reduced PCBs concentrations in plant roots by biochars show good linear relationship with those in TECAM

  6. Levels of PCBs, DDT, DDE and DDD in Italian human blood samples

    Energy Technology Data Exchange (ETDEWEB)

    Rocca, C. La; Abate, V.; Alivernini, S.; Iacovella, N.; Mantovani, A.; Turrio-Baldassarri, L. [Ist. Superiore di Sanita, Roma (Italy); Silvestroni, L.; Spera, G. [Dept. of Medical Pathophysiology, Univ. (Italy)

    2004-09-15

    The environmental contamination from polychlorinated biphenyls (PCBs) is effecting the exposure of the general population in a direct way through air inhalation, ingestion of particulate matter and dermal absorption and, most of all, in an indirect way through diet. Diet represents, in fact, the main way of human exposure to PCBs. PCBs have potential teratogenic, carcinogenic, hormonal and immunological effects. An association between endometriosis and high levels of PCB in plasma has also been reported3. Moreover, some congeners (PCB 105, PCB 118, PCB 153) have effects on thyroid hormones in animal models, although the PCB dose used in these experiments was an order of magnitude higher than the estimated human exposure. Humans are, however, exposed to a complex mixtures of PCB congeners. In this study identification and quantification of 60 PCB congeners and 3 chlorinated pesticides in human whole blood samples are presented. The subjects examined in this pilot study were a small group of patients with possible endocrine-related problems and unknown specific exposure. The aim of this study was to increase the present understanding about the distribution of the PCBs in human whole blood. The levels of DDT and metabolites were measured as well, since these compounds are consistently reported to contribute to the whole body burden of persistent chlorinated compounds, together with PCBs.

  7. Mineralization of PCBs by the genetically modified strain Cupriavidus necator JMS34 and its application for bioremediation of PCBs in soil

    Energy Technology Data Exchange (ETDEWEB)

    Saavedra, Juan Matias; Acevedo, Francisca; Gonzalez, Myriam; Seeger, Michael [Universidad Tecnica Federico Santa Maria, Valparaiso (Chile). Lab. de Microbiologia Molecular y Biotecnologia

    2010-07-15

    Polychlorobiphenyls (PCBs) are classified as ''high-priority pollutants''. Diverse microorganisms are able to degrade PCBs. However, bacterial degradation of PCBs is generally incomplete, leading to the accumulation of chlorobenzoates (CBAs) as dead-end metabolites. To obtain a microorganism able to mineralize PCB congeners, the bph locus of Burkholderia xenovorans LB400, which encodes one of the most effective PCB degradation pathways, was incorporated into the genome of the CBA-degrading bacterium Cupriavidus necator JMP134-X3. The bph genes were transferred into strain JMP134-X3, using the mini-Tn5 transposon system and biparental mating. The genetically modified derivative, C. necator strain JMS34, had only one chromosomal insertion of bph locus, which was stable under nonselective conditions. This modified bacterium was able to grow on biphenyl, 3-CBA and 4-CBA, and degraded 3,5-CBA in the presence of m-toluate. The strain JMS34 mineralized 3-CB, 4-CB, 2,4{sup '}-CB, and 3,5-CB, without accumulation of CBAs. Bioaugmentation of PCB-polluted soils with C. necator strain JMS34 and with the native B. xenovorans LB400 was monitored. It is noteworthy that strain JMS34 degraded, in 1 week, 99% of 3-CB and 4-CB and approximately 80% of 2,4{sup '}-CB in nonsterile soil, as well as in sterile soil. Additionally, the bacterial count of strain JMS34 increased by almost two orders of magnitude in PCB-polluted nonsterile soil. In contrast, the presence of native microflora reduced the degradation of these PCBs by strain LB400 from 73% (sterile soil) to approximately 50% (nonsterile soil). This study contributes to the development of improved biocatalysts for remediation of PCB-contaminated environments. (orig.)

  8. Life cycle of PCBs and contamination of the environment and of food products from animal origin.

    Science.gov (United States)

    Weber, Roland; Herold, Christine; Hollert, Henner; Kamphues, Josef; Ungemach, Linda; Blepp, Markus; Ballschmiter, Karlheinz

    2018-06-01

    This report gives a summary of the historic use, former management and current release of polychlorinated biphenyls (PCBs) in Germany and assesses the impact of the life cycle of PCBs on the contamination of the environment and of food products of animal origin. In Germany 60,000 t of PCBs were used in transformers, capacitors or as hydraulic oils. The use of PCB oils in these "closed applications", has been banned in Germany in 2000. Thirty to 50% of these PCBs were not appropriately managed. In West Germany, 24,000 t of PCBs were used in open applications, mainly as additive (plasticiser, flame retardant) in sealants and paints in buildings and other construction. The continued use in open applications has not been banned, and in 2013, an estimated more than 12,000 t of PCBs were still present in buildings and other constructions. These open PCB applications continuously emit PCBs into the environment with an estimated release of 7-12 t per year. This amount is in agreement with deposition measurements (estimated to 18 t) and emission estimates for Switzerland. The atmospheric PCB releases still have an relevant impact on vegetation and livestock feed. In addition, PCBs in open applications on farms are still a sources of contamination for farmed animals. Furthermore, the historic production, use, recycling and disposal of PCBs have contaminated soils along the lifecycle. This legacy of contaminated soils and contaminated feed, individually or collectively, can lead to exceedance of maximum levels in food products from animals. In beef and chicken, soil levels of 5 ng PCB-TEQ/kg and for chicken with high soil exposure even 2 ng PCB-TEQ/kg can lead to exceedance of EU limits in meat and eggs. Areas at and around industries having produced or used or managed PCBs, or facilities and areas where PCBs were disposed need to be assessed in respect to potential contamination of food-producing animals. For a large share of impacted land, management measures

  9. Dopamine plasma clearance is increased in piglets compared to neonates during continuous dopamine infusion

    DEFF Research Database (Denmark)

    Rasmussen, Martin B; Gramsbergen, Jan Bert; Eriksen, Vibeke Ramsgaard

    2018-01-01

    pharmacokinetics. METHODS: Arterial blood samples were drawn from six neonates admitted to the neonatal intensive care unit of Copenhagen University Hospital and 20 newborn piglets during continuous dopamine infusion. Furthermore, to estimate the piglet plasma dopamine half-life, blood samples were drawn at 2.......5-minute intervals after the dopamine infusion was discontinued. The plasma dopamine content was analysed by high-performance liquid chromatography with electrochemical detection. RESULTS: The dopamine displayed first-order kinetics in piglets and had a half-life of 2.5 minutes, while the median plasma...

  10. Effects of Methylphenidate on Resting-State Functional Connectivity of the Mesocorticolimbic Dopamine Pathways in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

    2013-08-01

    Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems–level effects of methylphenidate in this population have not yet been described. To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction.

  11. Ascorbic acid and striatal transport of [3H]1-methyl-4-phenylpyridine (MPP+) and [3H]dopamine

    International Nuclear Information System (INIS)

    Debler, E.A.; Hashim, A.; Lajtha, A.; Sershen, H.

    1988-01-01

    The inhibition of uptake of [ 3 H]dopamine and [ 3 H]1-methyl-4-phenylpyridine (MPP + ) was examined in mouse striatal synaptosomal preparations. Kinetic analysis indicated that ascorbic acid is a noncompetitive inhibitor of [ 3 H]MPP + uptake. No inhibition of [ 3 H]dopamine uptake is observed. The dopamine uptake blockers, GBR-12909, cocaine, and mazindol strongly inhibit (IC 50 3 H]dopamine and [ 3 H]MPP + transport. Nicotine, its metabolites, and other tobacco alkaloids are weak inhibitors except 4-phenylpyridine and lobeline, which are moderate inhibitors of both [ 3 H]dopamine and [ 3 H]MPP + uptake. These similarities in potencies are in agreement with the suggestion that [ 3 H]MPP + and [ 3 H] are transported by the same carrier. The differences observed in the alteration of dopaminergic transport and mazindol binding by ascorbic acid suggest that ascorbic acid's effects on [ 3 H]MPP + transport are related to translocation and/or dissociation processes occurring subsequent to the initial binding event

  12. Determination of potential sources of PCBs and PBDEs in sediments of the Niagara River

    Energy Technology Data Exchange (ETDEWEB)

    Samara, Fatin [Department of Chemistry, 611 Natural Science Complex, University at Buffalo, State University of New York, Buffalo, NY 14260-3000 (United States); Tsai, Christina W. [Department of Civil, Structural and Environmental Engineering, 233 Jarvis Hall, University at Buffalo, State University of New York, Buffalo, NY 14260-4400 (United States); Aga, Diana S. [Department of Chemistry, 611 Natural Science Complex, University at Buffalo, The State University of New York, Buffalo, NY 14260-3000 (United States)]. E-mail: dianaaga@buffalo.edu

    2006-02-15

    Sediments from Niagara River, an important waterway connecting two of the Great Lakes (Lake Erie to Lake Ontario), were analyzed for 14 congeners of polychlorinated biphenyls (PCBs) and 9 congeners of polybrominated diphenyl ethers (PBDEs) using accelerated solvent extraction and gas chromatography/mass spectrometry. Total concentrations of PCBs ranged from 1.7 to 124.6 ng/g were PCBs 138 and 153 were found in all samples. All sites but one showed PBDE in sediments with total concentrations as high as 148 ng/g, suggesting that PBDE is becoming an important class of POP. A land-use and coverage map was used to trace potential localized sources of PCB and PBDE contamination. Results indicate that the highest levels of PCBs and PBDEs were found in sediments collected from areas closest to the discharge locations of municipal wastewater treatment plants (WWTP) and local industries. This is the first study that suggests the importance of WWTP discharges as a potential source of PBDE contamination in the Great Lakes. - Wastewater treatment plant discharges are a main source of PCBs and PBDEs to Niagara River sediments.

  13. Interactions between aromatase (estrogen synthase) and dopamine in the control of male sexual behavior in quail.

    Science.gov (United States)

    Balthazart, Jacques; Baillien, Michelle; Ball, Gregory F

    2002-05-01

    In male quail, like in other vertebrates including rodents, testosterone acting especially through its estrogenic metabolites is necessary for the activation of male sexual behavior. Also, the administration of dopamine agonists and antagonists profoundly influences male sexual behavior. How the steroid-sensitive neural network and dopamine interact physiologically, remains largely unknown. It is often implicitly assumed that testosterone or its metabolite estradiol, stimulates male sexual behavior via the modification of dopaminergic transmission. We have now identified in quail two possible ways in which dopamine could potentially affect sexual behavior by modulating the aromatization of testosterone into an estrogen. One is a long-acting mechanism that presumably involves the modification of dopaminergic transmission followed by the alteration of the genomic expression of aromatase. The other is a more rapid mechanism that does not appear to be dopamine receptor-mediated and may involve a direct interaction of dopamine with aromatase (possibly via substrate competition). We review here the experimental data supporting the existence of these controls of aromatase activity by dopamine and discuss the possible contribution of these controls to the activation of male sexual behavior.

  14. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

    Science.gov (United States)

    Dietrich, Marcelo O; Bober, Jeremy; Ferreira, Jozélia G; Tellez, Luis A; Mineur, Yann S; Souza, Diogo O; Gao, Xiao-Bing; Picciotto, Marina R; Araújo, Ivan; Liu, Zhong-Wu; Horvath, Tamas L

    2012-01-01

    It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit–impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing–dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors. PMID:22729177

  15. Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

    Science.gov (United States)

    Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

    2007-11-01

    Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

  16. Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine.

    Science.gov (United States)

    Baldwin, H A; Colado, M I; Murray, T K; De Souza, R J; Green, A R

    1993-03-01

    1. Administration to rats of methamphetamine (15 mg kg-1, i.p.) every 2 h to a total of 4 doses resulted in a neurotoxic loss of striatal dopamine of 36% and of 5-hydroxytryptamine (5-HT) in the cortex (43%) and hippocampus (47%) 3 days later. 2. Administration of chlormethiazole (50 mg kg-1, i.p.) 15 min before each dose of methamphetamine provided complete protection against the neurotoxic loss of monoamines while administration of dizocilpine (1 mg kg-1, i.p.) using the same dose schedule provided substantial protection. 3. Measurement of dopamine release in the striatum by in vivo microdialysis revealed that methamphetamine produced an approximate 7000% increase in dopamine release after the first injection. The enhanced release response was somewhat diminished after the third injection but still around 4000% above baseline. Dizocilpine (1 mg kg-1, i.p.) did not alter this response but chlormethiazole (50 mg kg-1, i.p.) attenuated the methamphetamine-induced release by approximately 40%. 4. Dizocilpine pretreatment did not influence the decrease in the dialysate concentration of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) produced by administration of methamphetamine while chlormethiazole pretreatment decreased the dialysate concentration of these metabolites still further. 5. The concentration of dopamine in the dialysate during basal conditions increased modestly during the course of the experiment. This increase did not occur in chlormethiazole-treated rats. HVA concentrations were unaltered by chlormethiazole administration. 6. Chlormethiazole (100-1000 microM) did not alter methamphetamine (100 microM) or K+ (35 mM)-evoked release of endogenous dopamine from striatal prisms in vitro. 7. Several NMDA antagonists prevent methamphetamine-induced neurotoxicity; however chlormethiazole is not an NMDA antagonist. Inhibition of striatal dopamine function prevents methamphetamine-induced toxicity of both dopamine and 5

  17. New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

    Directory of Open Access Journals (Sweden)

    Albert C. Yang

    2017-08-01

    Full Text Available Schizophrenia has been primarily associated with dopamine dysfunction, and treatments have been developed that target the dopamine pathway in the central nervous system. However, accumulating evidence has shown that the core pathophysiology of schizophrenia might involve dysfunction in dopaminergic, glutamatergic, serotonergic, and gamma-aminobutyric acid (GABA signaling, which may lead to aberrant functioning of interneurons that manifest as cognitive, behavioral, and social dysfunction through altered functioning of a broad range of macro- and microcircuits. The interactions between neurotransmitters can be modeled as nodes and edges by using graph theory, and oxidative balance, immune, and glutamatergic systems may represent multiple nodes interlocking at a central hub; imbalance within any of these nodes might affect the entire system. Therefore, this review attempts to address novel treatment targets beyond the dopamine hypothesis, including glutamate, serotonin, acetylcholine, GABA, and inflammatory cytokines. Furthermore, we outline that these treatment targets can be possibly integrated with novel treatment strategies aimed at different symptoms or phases of the illness. We anticipate that reversing anomalous activity in these novel treatment targets or combinations between these strategies might be beneficial in the treatment of schizophrenia.

  18. Epigenetic dysregulation of the dopamine system in diet-induced obesity.

    Science.gov (United States)

    Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

    2012-03-01

    Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  19. 40 CFR 129.105 - Polychlorinated biphenyls (PCBs).

    Science.gov (United States)

    2010-07-01

    ... dielectric. (3) Electrical transformer manufacturer means a manufacturer who produces or assembles electrical... manufacturer. (d) Electrical transformer manufacturer—(1) Applicability. (i) These standards or prohibitions... are prohibited in any discharge from any electrical transformer manufacturer; (ii) New sources. PCBs...

  20. NEW DOPAMINE AGONISTS IN CARDIOVASCULAR THERAPY

    NARCIS (Netherlands)

    GIRBES, ARJ; VANVELDHUISEN, DJ; SMIT, AJ

    1992-01-01

    Dopamine, a naturally occurring catecholamine, has been extensively used in intensive care for many years. Dopamine stimulates different types of adrenergic receptors: alpha-1 and -2, beta-1 and -2, and dopamine-1 and -2. The renal effects of dopamine are the result of dopamine-1 receptor (DA1)

  1. Infralimbic dopamine D2 receptors mediate glucocorticoid-induced facilitation of auditory fear memory extinction in rats.

    Science.gov (United States)

    Dadkhah, Masoumeh; Abdullahi, Payman Raise; Rashidy-Pour, Ali; Sameni, Hamid Reza; Vafaei, Abbas Ali

    2018-03-01

    The infralimbic (IL) cortex of the medial prefrontal cortex plays an important role in the extinction of fear memory. Also, it has been showed that both brain glucocorticoid and dopamine receptors are involved in many processes such as fear extinction that drive learning and memory; however, the interaction of these receptors in the IL cortex remains unclear. We examined a putative interaction between the effects of glucocorticoid and dopamine receptors stimulation in the IL cortex on fear memory extinction in an auditory fear conditioning paradigm in male rats. Corticosterone (the endogenous glucocorticoid receptor ligand), or RU38486 (the synthetic glucocorticoid receptor antagonist) microinfusion into the IL cortex 10 min before test 1 attenuated auditory fear expression at tests 1-3, suggesting as an enhancement of fear extinction. The effect of corticosterone, but not RU38486 was counteracted by the dopamine D2 receptor antagonist sulpiride pre-treatment administered into the IL (at a dose that failed to alter freezing behavior on its own). In contrast, intra-IL infusion of the dopamine D1 receptor antagonist SCH23390 pre-treatment failed to alter freezing behavior. These findings provide evidence for the involvement of the IL cortex D2 receptors in CORT-induced facilitation of fear memory extinction. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Dopamine D2 receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse

    OpenAIRE

    Oien, Derek B.; Ortiz, Andrea N.; Rittel, Alexander G.; Dobrowsky, Rick T.; Johnson, Michael A.; Levant, Beth; Fowler, Stephen C.; Moskovitz, Jackob

    2010-01-01

    Previous research suggests that brain oxidative stress and altered rodent locomotor behavior are linked. We observed bio-behavioral changes in methionine sulfoxide reductase A knockout mice associated with abnormal dopamine signaling. Compromised ability of these knockout mice to reduce methionine sulfoxide enhances accumulation of sulfoxides in proteins. We examined the dopamine D2-receptor function and expression, which has an atypical arrangement and quantity of methionine residues. Indeed...

  3. Polychlorinated biphenyl-induced alterations of thyroid hormone homeostasis and brain development in the rat

    NARCIS (Netherlands)

    Morse, D.C.

    1995-01-01

    Introduction

    The work described in this thesis was undertaken to gain insight in the processes involved in the developmental neurotoxicity of polychlorinated biphenyls. It has been previously hypothesized that the alteration of thyroid hormone status by PCBs may

  4. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  5. The Behavioral Pharmacology of Effort-Related Choice Behavior: Dopamine, Adenosine and beyond

    Science.gov (United States)

    Salamone, John D.; Correa, Merce; Nunes, Eric J.; Randall, Patrick A.; Pardo, Marta

    2012-01-01

    For many years, it has been suggested that drugs that interfere with dopamine (DA) transmission alter the "rewarding" impact of primary reinforcers such as food. Research and theory related to the functions of mesolimbic DA are undergoing a substantial conceptual restructuring, with the traditional emphasis on hedonia and primary reward yielding…

  6. Dopamine induces neutrophil apoptosis through a dopamine D-1 receptor-independent mechanism.

    LENUS (Irish Health Repository)

    Sookhai, S

    2012-02-03

    BACKGROUND: For the normal resolution of an acute inflammatory response, neutrophil (PMN) apoptosis is essential to maintain immune homeostasis and to limit inappropriate host tissue damage. A delay in PMN apoptosis has been implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS). Dopamine, a biogenic amine with known cardiovascular and neurotransmitter properties, is used in patients with SIRS to maintain hemodynamic stability. We sought to determine whether dopamine may also have immunoregulatory properties capable of influencing PMN apoptosis, function, and activation state in patients with SIRS. METHODS: PMNs were isolated from healthy volunteers and patients with SIRS and treated with varying doses of dopamine and a dopamine D-1 receptor agonist, fenoldopam. PMN apoptosis was assessed every 6 hours with use of propidium iodide DNA staining and PMN function was assessed with use of respiratory burst activity, phagocytosis ability, and CD11a, CD11b, and CD18 receptor expression as functional markers. RESULTS: There was a significant delay in PMN apotosis in patients with SIRS compared with controls. Treatment of isolated PMNs from both healthy controls and patients with SIRS with 10 and 100 mumol\\/L dopamine induced apoptosis. PMN ingestive and cytocidal capacity were both decreased in patients with SIRS compared with controls. Treatment with dopamine significantly increased phagocytic function. Fenoldopam did not induce PMN apoptosis. CONCLUSION: Our data demonstrate for the first time that dopamine induces PMN apoptosis and modulates PMN function both in healthy controls and in patients with SIRS. These results indicate that dopamine may be beneficial during SIRS through a nonhemodynamic PMN-dependent proapoptotic mechanism.

  7. Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway.

    Directory of Open Access Journals (Sweden)

    Tertia D Purves-Tyson

    receptor-driven events as estradiol had minimal effect. We conclude that nigrostriatal responsivity to dopamine may be modulated by testosterone acting via androgen receptors to alter gene expression of molecules involved in dopamine signaling during adolescence.

  8. Estradiol increases the sensitivity of ventral tegmental area dopamine neurons to dopamine and ethanol.

    Directory of Open Access Journals (Sweden)

    Bertha J Vandegrift

    Full Text Available Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2, the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2 or estrus (low E2 for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780 reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission.

  9. Electrokinetic delivery of persulfate to remediate PCBs polluted soils: effect of injection spot.

    Science.gov (United States)

    Fan, Guangping; Cang, Long; Fang, Guodong; Qin, Wenxiu; Ge, Liqiang; Zhou, Dongmei

    2014-12-01

    Persulfate-based in situ chemical oxidation (ISCO) is a promising technique for the remediation of organic compounds contaminated soils. Electrokinetics (EK) provides an alternative method to deliver oxidants into the target zones especially in low permeable-soil. In this study, the flexibility of delivering persulfate by EK to remediate polychlorinated biphenyls (PCBs) polluted soil was investigated. 20% (w/w) of persulfate was injected at the anode, cathode and both electrodes to examine its transport behaviors under electrical field, and the effect of field inversion process was also evaluated. The results showed that high dosage of persulfate could be delivered into S4 section (near cathode) by electroosmosis when persulfate was injected from anode, 30.8% of PCBs was removed from the soil, and the formed hydroxyl precipitation near the cathode during EK process impeded the transportation of persulfate. In contrast, only 18.9% of PCBs was removed with the injection of persulfate from cathode, although the breakthrough of persulfate into the anode reservoir was observed. These results indicated that the electroosmotic flow is more effective for the transportation of persulfate into soil. The addition of persulfate from both electrodes did not significantly facilitate the PCBs oxidation as well as the treatment of electrical field reversion, the reinforced negative depolarization function occurring in the cathode at high current consumed most of the oxidant. Furthermore, it was found that strong acid condition near the anode favored the oxidation of PCBs by persulfate and the degradation of PCBs was in consistent with the oxidation of Soil TOC in EK/persulfate system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Behavior and source characteristic of PCBS in urban ambient air of Yokohama, Japan

    International Nuclear Information System (INIS)

    Kim, Kyoung-Soo; Masunaga, Shigeki

    2005-01-01

    To understand the behavior and sources of polychlorinated biphenyls (PCBs) in ambient air, gaseous and particulate phase concentrations were measured at Yokohama City, Japan, during March 2002 and February 2003. The concentration of total PCB and TEQ ranged from 62 to 250 pg/m 3 and from 2 to 14 fgTEQ/m 3 , respectively. The gas-particle partition coefficient (K p ) was obtained as a function of temperature. The relationship between the partition coefficient and the sub-cooled liquid vapor pressure (P L ) was also established (coefficients of determination for log K p versus log P L plot were >0.76, except for three samples). As a result, the partition ratio of gaseous and particulate phase PCBs can be estimated for an arbitrary temperature. Principal component analysis (PCA) was applied to the source identification of PCBs in ambient air. The concentrations of 122 congeners between tetra-CBs and deca-CB were used as input variables, and three PCs with eigenvalue more than 10 were obtained. The principal component 1 (PC 1) accounted for 43.4% of the total variance, and was interpreted as volatilization from PCB products and/or sites polluted by PCBs. The concentrations of PCB congeners were strongly related with PC 1 which showed high correlation with temperature. PC 2 accounted for 22.3%, and was interpreted as PCBs from incineration sources, while PC 3 accounted for 10.8%, but could not be interpreted. - The relationship between the gas-particle partition coefficient (K p ) and sub-cooled liquid vapor pressure was estimated using gaseous and particle phase concentration in ambient air, and was estimated source apportionment of PCBs

  11. Central GLP-1 receptor activation modulates cocaine-evoked phasic dopamine signaling in the nucleus accumbens core.

    Science.gov (United States)

    Fortin, Samantha M; Roitman, Mitchell F

    2017-07-01

    Drugs of abuse increase the frequency and magnitude of brief (1-3s), high concentration (phasic) dopamine release events in terminal regions. These are thought to be a critical part of drug reinforcement and ultimately the development of addiction. Recently, metabolic regulatory peptides, including the satiety signal glucagon-like peptide-1 (GLP-1), have been shown to modulate cocaine reward-driven behavior and sustained dopamine levels after cocaine administration. Here, we use fast-scan cyclic voltammetry (FSCV) to explore GLP-1 receptor (GLP-1R) modulation of dynamic dopamine release in the nucleus accumbens (NAc) during cocaine administration. We analyzed dopamine release events in both the NAc shell and core, as these two subregions are differentially affected by cocaine and uniquely contribute to motivated behavior. We found that central delivery of the GLP-1R agonist Exendin-4 suppressed the induction of phasic dopamine release events by intravenous cocaine. This effect was selective for dopamine signaling in the NAc core. Suppression of phasic signaling in the core by Exendin-4 could not be attributed to interference with cocaine binding to one of its major substrates, the dopamine transporter, as cocaine-induced increases in reuptake were unaffected. The results suggest that GLP-1R activation, instead, exerts its suppressive effects by altering dopamine release - possibly by suppressing the excitability of dopamine neurons. Given the role of NAc core dopamine in the generation of conditioned responses based on associative learning, suppression of cocaine-induced dopamine signaling in this subregion by GLP-1R agonism may decrease the reinforcing properties of cocaine. Thus, GLP-1Rs remain viable targets for the treatment and prevention of cocaine seeking, taking and relapse. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Toxicity and biodegradation of PCBs in contaminated sediments

    International Nuclear Information System (INIS)

    Dercova, K.; Cicmanova, J.; Lovecka, P.; Demnerova, K.; Mackova, M.; Hucko, P.; Kusnir, P.

    2006-01-01

    PCBs represent a serious ecological problem due to their low degradability, high toxicity, and strong bioaccumulation. Because of many environmental and economical problems, there are efforts to develop bio-remediation technologies for decontamination of the PCB-polluted areas. PCB were used by storage of spent nuclear fuel in nuclear power plants Jaslovske Bohunice. In the locality of the former producer of PCB - Chemko Strazske a. s. - big amount of these substances is still persisting in sediments and soil. The goal of this study was to analyze the contaminated sediments from Strazsky canal and Zemplinska Sirava water reservoir from several points of view. The study of eco-toxicity confirmed that both sediments were toxic for various tested organisms. The genotoxicity test has not proved the mutagenic effect. The subsequent step included microbiological analysis of the contaminated sediments and isolation of pure bacterial cultures capable of degrading PCBs. In order to determine the genetic potential for their biodegradability, the gene bphA1 was identified using PCR technique in their genomes. This gene codes the enzyme biphenyl-dioxygenase, which is responsible for PCB degradation. The final goal was to perform aerobic biodegradation of PCBs in the sediments. The bacteria present in both sediments are able to degrade certain low chlorinated congeners. The issue of biodiversity is still open and has to be studied to reveal the real cooperation between bacteria. (authors)

  13. Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.

    Science.gov (United States)

    Perez, Stephanie M; Lodge, Daniel J

    2012-11-01

    Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

  14. Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta

    DEFF Research Database (Denmark)

    Virtanen, H E; Koskenniemi, J J; Sundqvist, E

    2012-01-01

    In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case-control study has reported an association...... between congenital cryptorchidism and colostrum PCB levels. We performed a case-control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels...... controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases...

  15. Review on occurrence and behavior of PCDD/Fs and dl-PCBs in atmosphere of East Asia

    Science.gov (United States)

    Trinh, Minh Man; Chang, Moo Been

    2018-05-01

    This paper reviews the data from studies mainly published after 2000 to provide the current understanding of the physicochemical properties, atmospheric occurrence, gas/particle partitioning, fate and temporal trends in atmospheric matrix of PCDD/Fs and dl-PCBs of East Asia. Ambient PCDD/Fs and dl-PCBs concentrations in East Asia are found to be tens to hundreds times higher than that measured in Europe and North America. After strict regulations on PCDD/Fs and dl-PCBs emissions are enacted, the concentrations of these compounds decrease dramatically in Eastern Asian countries. In general, most of PCDD/Fs distribute in particle phase while dl-PCBs majorly exist in gas phase. Three main factors including physicochemical properties of the compounds, properties of particle and atmospheric condition affect the gas/particle partitioning of PCDD/Fs and dl-PCBs. The accuracy of absorption and adsorption models on predicting gas/particle partitioning of PCDD/Fs and dl-PCBs is evaluated. Gas-phase compounds are mostly removed from the atmosphere via reactions with OH radicals while those in particle phase are majorly removed by wet/dry deposition processes. The effects of removing processes and long-range transport on gas/particle partitioning are also discussed.

  16. Painted surfaces - Important sources of polychlorinated biphenyls (PCBs) contamination to the urban and marine environment

    International Nuclear Information System (INIS)

    Jartun, Morten; Ottesen, Rolf Tore; Steinnes, Eiliv; Volden, Tore

    2009-01-01

    A study of a large number of samples of flaking old paint from various buildings in Bergen, Norway (N = 68) suggests that paint may be the most important contemporary source of PCBs in this urban environment with concentrations of PCB 7 up to 3.39 g/kg. Twenty-three of the samples were collected from a single building, and the concentrations were found to vary over 3 orders of magnitude. In addition, 16 concrete samples from a large bridge previously coated with PCB-containing paint were collected and separated into outer- and inner samples indicating that PCBs are still present in high concentrations subsequent to renovation. PCBs were found in several categories of paint from wooden and concrete buildings, potentially introduced to the environment by natural weathering, renovation, and volatilization. Consequently, this dispersion may lead to increased levels of PCBs in urban atmospheres, soils, and harbor sediments where high concentrations have resulted in Governmental advice against consumption of certain seafood. - Paint from structures built during the period 1950-1970 may be the most important source of PCBs in an urban environment

  17. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease.

    Science.gov (United States)

    Dunn, Amy R; Stout, Kristen A; Ozawa, Minagi; Lohr, Kelly M; Hoffman, Carlie A; Bernstein, Alison I; Li, Yingjie; Wang, Minzheng; Sgobio, Carmelo; Sastry, Namratha; Cai, Huaibin; Caudle, W Michael; Miller, Gary W

    2017-03-14

    Members of the synaptic vesicle glycoprotein 2 (SV2) family of proteins are involved in synaptic function throughout the brain. The ubiquitously expressed SV2A has been widely implicated in epilepsy, although SV2C with its restricted basal ganglia distribution is poorly characterized. SV2C is emerging as a potentially relevant protein in Parkinson disease (PD), because it is a genetic modifier of sensitivity to l-DOPA and of nicotine neuroprotection in PD. Here we identify SV2C as a mediator of dopamine homeostasis and report that disrupted expression of SV2C within the basal ganglia is a pathological feature of PD. Genetic deletion of SV2C leads to reduced dopamine release in the dorsal striatum as measured by fast-scan cyclic voltammetry, reduced striatal dopamine content, disrupted α-synuclein expression, deficits in motor function, and alterations in neurochemical effects of nicotine. Furthermore, SV2C expression is dramatically altered in postmortem brain tissue from PD cases but not in Alzheimer disease, progressive supranuclear palsy, or multiple system atrophy. This disruption was paralleled in mice overexpressing mutated α-synuclein. These data establish SV2C as a mediator of dopamine neuron function and suggest that SV2C disruption is a unique feature of PD that likely contributes to dopaminergic dysfunction.

  18. PCBs determination in water, soils and biota by perchlorination and GC-ECD

    Energy Technology Data Exchange (ETDEWEB)

    Feshin, D. [Institute of Ecology and Evolution RAS, Moscow (Russian Federation); Klyuev, N.; Brodsky, E.; Kalinkevich, G.

    2004-09-15

    Most of the PCB pollutions are caused by industrial application. PCB-containing mixtures whose compositions are well known and constant should be rapidly and precisely analyzable as total PCB to monitor real pollution exposure. Consequently, a simple but reproducible and cheap method for operative control is needed which should be periodically controlled by standard analytical methods. So it is advisable to have a rapid method that will allow PCBs determination in wide range of quantities by simple instrumentation with internal standards. The method based on perchlorination of PCBs considerably simplifies the detection of PCB congeners as compared to other techniques. In this practice all polychlorinated derivatives are converted into decachlorobiphenyl (DCB). This is followed by gas chromatography with electron capture detector (GC-ECD), which is highly sensitive for the substances of interest. Currently EPA procedure 508a (1989) is the only official screening method for detection of PCBs using perchlorination. This uses SbCl5 and powdered Fe mixture as reagent at 270 C without internal standard. We reported about using of perchlorination reagent based on mixture of powdered duralumin, sulphur and SO2Cl2 heated at 105 C for 2 h for detection of PCBs as decachlorobiphenyls in a wide range of concentration: 16.4 ng/sample to 164 {mu}/sample. 4,4'-difluorobiphenyl was proposed as internal standard that allowed to control all steps of sample preparation including perchlorination reaction. In the present work we extended our experience of perchlorination to detect the PCBs.

  19. Identifying polymorphisms in the Rattus norvegicus D3 dopamine receptor gene and regulatory region

    NARCIS (Netherlands)

    Smits, B.M.; D'Souza, U.M.; Berezikov, E.; Cuppen, E.; Sluyter, F.

    2004-01-01

    The D(3) dopamine receptor has been implicated in several neuropsychiatric disorders, including schizophrenia, Parkinson's disease and addiction. Sequence variation in the D(3) gene can lead to subtle alteration in receptor structure or gene expression and thus to a different phenotype. In this

  20. Dopamine, reward learning, and active inference.

    Science.gov (United States)

    FitzGerald, Thomas H B; Dolan, Raymond J; Friston, Karl

    2015-01-01

    Temporal difference learning models propose phasic dopamine signaling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behavior. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings.

  1. Dietary intake of dioxins, furans and dioxin-like PCBs in Austria.

    Science.gov (United States)

    Rauscher-Gabernig, Elke; Mischek, Daniela; Moche, Wolfgang; Prean, Michael

    2013-01-01

    Human exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like PCBs (dl-PCBs) should be assessed regularly. In order to evaluate the contamination levels in various food products on the Austrian market and to assess the dietary exposure of the Austrian population for the first time, a national monitoring programme was conducted from 2005 to 2011. The 235 food products comprised meat, poultry, game and offal, fish and fish products, milk and dairy products, eggs, animal fats and vegetable oils. To estimate the dietary intakes of PCDD/Fs and dl-PCBs, mean concentrations in food were combined with the respective food consumption data from the Austrian food consumption survey. Estimated dietary intakes were expressed as toxic equivalents (WHO-TEQs 1998). The mean intakes for PCDD/Fs and dl-PCBs were estimated as 0.77, 0.75 and 0.61 pg WHO-TEQ kg(-1) bw day(-1) for children, women and men, respectively. The main contributors to total intake were milk and dairy products followed by fish and fish products for children and women, and meat, poultry, game and offal for men (65% and 15% for children, 67% and 14% for women, and 63% and 19% for men, respectively). Comparison of the estimated dietary intakes with the toxicological reference values shows that both children and adults are well below those values.

  2. Pharmacological characterization of the dopamine-sensitive adenylate cyclase in cockroach brain: evidence for a distinct dopamine receptor

    International Nuclear Information System (INIS)

    Orr, G.L.; Gole, J.W.D.; Notman, H.J.; Downer, R.G.H.

    1987-01-01

    Dopamine increases cyclic AMP production in crude membrane preparations of cockroach brain with plateaus in cyclic AMP production occurring between 1-10 μM and 10 mM. Maximal production of cyclic AMP is 2.25 fold greater than that of control values. Octopamine also increases cyclic AMP production with a Ka of 1.4 μM and maximal production 3.5 fold greater than that of control. 5-Hydroxytryptamine does not increase cyclic AMP production. The effects of octopamine and dopamine are fully additive. The vertebrate dopamine agonists ADTN and epinine stimulate the dopamine-sensitive adenylate cyclase (AC) with Ka values of 4.5 and 0.6 μM respectively and with maximal effectiveness 1.7 fold greater than that of control. The selective D 2 -dopamine agonist LY-171555 stimulates cyclic AMP production to a similar extent with a Ka of 50 μM. Other dopamine agonists have no stimulatory effects. With the exception of mianserin, 3 H-piflutixol is displaced from brain membranes by dopamine antagonists with an order of potency similar to that observed for the inhibition of dopamine-sensitive AC. The results indicate that the octopamine- and dopamine-sensitive AC in cockroach brain can be distinguished pharmacologically and the dopamine receptors coupled to AC have pharmacological characteristics distinct from vertebrate D 1 - and D 2 -dopamine receptors. 33 references, 3 figures, 2 tables

  3. Atmospheric concentration characteristics and gas-particle partitioning of PCBs in a rural area of eastern Germany

    International Nuclear Information System (INIS)

    Mandalakis, Manolis; Stephanou, Euripides G.

    2007-01-01

    Atmospheric concentrations of polychlorinated biphenyls (PCBs) were measured in 14 successive daytime and nighttime air samples collected from Melpitz, a rural site in eastern Germany. The average total concentration of PCBs was 110+/-80pgm -3 and they were predominately present in the gas phase (∼95%). Composition of individual congeners closely resembled those of Clophen A30 and Aroclor 1232. Partial vapor pressures of PCBs were well correlated with temperature and the steep slopes obtained from Clausius-Clapeyron plots (-4500 to -8000) indicated that evaporation from adjacent land surfaces still controls the atmospheric levels of these pollutants. Particle-gas partitioning coefficients (K P ) of PCBs were well correlated with the respective sub-cooled vapor pressures (P L o ), but the slopes obtained from logK P versus logP L o plots (-0.16 to -0.59) deviated significantly from the expected value of -1. Overall, gas-particle partitioning of PCBs was better simulated by Junge-Pankow than octanol/air partition coefficient-based model

  4. The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats

    International Nuclear Information System (INIS)

    Bunaciu, Rodica Petruta; Tharappel, Job C.; Lehmler, Hans-Joachim; Kania-Korwel, Izabela; Robertson, Larry W.; Srinivasan, Cidambi; Spear, Brett T.; Glauert, Howard P.

    2007-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitious lipophilic environmental pollutants. Some of the PCB congeners and mixtures of congeners have tumor promoting activity in rat liver. The mechanism of their activity is not fully understood and is likely to be multifactorial. The aim of this study was to investigate if the resident liver macrophages, Kupffer cells, are important in the promoting activity of PCBs. The hypothesis of this study was that the inhibition of Kupffer cell activity would inhibit hepatic tumor promotion by PCBs in rats. To test our hypothesis, we studied the effects of Kupffer cell inhibition by dietary glycine (an inhibitor of Kupffer cell secretory activity) in a rat two-stage hepatocarcinogenesis model using 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153, a non-dioxin-like PCB) or 3,3',4,4'-tetrachlorobiphenyl (PCB-77, a dioxin-like PCB) as promoters. Diethylnitrosamine (DEN, 150 mg/kg) was administered to female Sprague-Dawley rats, which were then placed on an unrefined diet containing 5% glycine (or casein as nitrogen control) starting two weeks after DEN administration. On the third day after starting the diets, rats received PCB-77 (300 μmol/kg), PCB-153 (300 μmol/kg), or corn oil by i.p. injection. The rats received a total of 4 PCB injections, administered every 14 days. The rats were euthanized on the 10th day after the last PCB injection, and the formation of altered hepatic foci expressing placental glutathione S-transferase (PGST) and the rate of DNA synthesis in these foci and in the normal liver tissue were determined. Glycine did not significantly affect foci number or volume. PCB-153 did not significantly increase the focal volume, but increased the number of foci per liver, but only in the rats not fed glycine; PCB-77 increased both the foci number and their volume in both glycine-fed and control rats. Glycine did not alter the PCB content of the liver, but did increase the activity of 7-benzyloxyresorufin O-dealkylase (BROD

  5. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

    Directory of Open Access Journals (Sweden)

    Jessica M. V. Pino

    2017-05-01

    Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

  6. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Donald A., E-mail: dafox@uh.edu [College of Optometry, University of Houston, Houston, TX (United States); Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX (United States); Hamilton, W. Ryan [Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Johnson, Jerry E. [Department of Natural Sciences, University of Houston-Downtown, Houston, TX (United States); Xiao, Weimin [College of Optometry, University of Houston, Houston, TX (United States); Chaney, Shawntay; Mukherjee, Shradha [Department of Biology and Biochemistry, University of Houston, Houston, TX (United States); Miller, Diane B.; O' Callaghan, James P. [Toxicology and Molecular Biology Branch, Health Effects Research Laboratory, Centers for Disease Control and Prevention-NIOSH, Morgantown, WV USA (United States)

    2011-11-15

    -Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased the number of TH-immunoreactive dopaminergic amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure selectively decreased dopaminergic, but not GABAergic, glycinergic or cholinergic, amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased retinal dopamine content, its metabolites and dopamine utilization Black-Right-Pointing-Pointer A decrease in dopamine can alter ERG amplitudes, circadian rhythms, dark/light adaptation and spatial contrast sensitivity.

  7. Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice

    International Nuclear Information System (INIS)

    Fox, Donald A.; Hamilton, W. Ryan; Johnson, Jerry E.; Xiao, Weimin; Chaney, Shawntay; Mukherjee, Shradha; Miller, Diane B.; O'Callaghan, James P.

    2011-01-01

    -immunoreactive dopaminergic amacrine cells ► Gestational lead exposure selectively decreased dopaminergic, but not GABAergic, glycinergic or cholinergic, amacrine cells ► Gestational lead exposure dose-dependently decreased retinal dopamine content, its metabolites and dopamine utilization ► A decrease in dopamine can alter ERG amplitudes, circadian rhythms, dark/light adaptation and spatial contrast sensitivity

  8. Phasic Mesolimbic Dopamine Signaling Encodes the Facilitation of Incentive Motivation Produced by Repeated Cocaine Exposure

    OpenAIRE

    Ostlund, SB; LeBlanc, KH; Kosheleff, AR; Wassum, KM; Maidment, NT

    2014-01-01

    Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the curr...

  9. Dopamine, reward learning, and active inference

    Directory of Open Access Journals (Sweden)

    Thomas eFitzgerald

    2015-11-01

    Full Text Available Temporal difference learning models propose phasic dopamine signalling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behaviour. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings.

  10. Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

    Science.gov (United States)

    Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

    2017-02-01

    There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

  11. Levels of dioxins and dioxin-like PCBs in food and feed in Europe

    Energy Technology Data Exchange (ETDEWEB)

    Gallani, B.; Verstraete, F. [European Commission, DG SANCO, Brussels (Belgium); Boix, A.; Holst, C. von; Anklam, E. [European Commission, Joint Research Centre, Geel (Belgium)

    2004-09-15

    Regulation (EC) No 466/2001 as amended by Council Regulation (EC) No 2375/2001 of November 2001 setting maximum levels for certain contaminants in foodstuffs, inter alia dioxins, stipulates that foodstuffs should not, when placed on the market, contain higher contaminant levels than those specified in that Regulation. The Regulation also states that the Commission shall review Section 5 of Annex I, which outlines the maximum levels for dioxins and furans in food, by 31 December 2004 at the latest, in the light of new data on the presence of dioxins and dioxin-like PCBs, in particular with a view to the inclusion of dioxin-like PCBs in the levels to be set. Section 5 of Annex I shall be further reviewed by 31 December 2006 at the latest with the aim of significantly reducing the maximum levels. An EC Recommended Monitoring Programme for Food (Ref 1) was discussed to provide the Commission with the necessary data to make it possible to meet these commitments. A considerable amount of data was received by the Commission on the occurrence of dioxins and dioxin-like PCBs in food and was analysed to determine whether any patterns emerge in the ratios between dioxins and dioxin-like PCBs in certain food types or in certain areas. Directive 2002/32/EC of the European Parliament and of the Council as amended by Commission Directive 2003/57/EC of 17 June 2003 on undesirable substances in animal feed establishes maximum levels for dioxins in several feed materials and compound feeding stuffs. Similar revision clauses to the Regulation on food apply to this Directive on feeding stuffs. A monitoring programme similar to the one recommended for food was discussed for undesirable substances in animal feed (Ref 2). Data submitted by Member states on the occurrence of dioxins and dioxin-like PCBs in feed have also been analysed to determine whether any patterns emerge in the ratios between dioxins and dioxin-like PCBs in certain feedstuffs or in certain areas. This paper describes

  12. A baseline study on levels of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, non-ortho and mono-ortho PCBs, non-dioxin-like PCBs and polybrominated diphenyl ethers in Northeast Arctic cod (Gadus morhua) from different parts of the Barents Sea

    International Nuclear Information System (INIS)

    Julshamn, Kaare; Duinker, Arne; Berntssen, Marc; Nilsen, Bente M.; Frantzen, Sylvia; Nedreaas, Kjell; Maage, Amund

    2013-01-01

    Highlights: • Livers of cod from the Barents Sea have been analysed for dioxins, PCBs and PBDEs. • The overall mean concentration of dioxins and DL-PCBs was 14.2 ng TEQ WHO-2005 /kg ww. • The concentrations of dioxins and DL-PCBs varied between 1.0 and 151 ng TEQ/kg ww. • 20% of the samples had concentrations higher than 20 ng TEQ/kg ww. • The highest concentrations of dioxins and PCB were found in samples from the east area of the Barents Sea. -- Abstract: This study is one of several baseline studies on commercially important Norwegian wild fish species that will provide information concerning metals and persistent organic pollutants (POPs) and food safety. The cod liver is a traditional food product in Norway and a potential source for POPs in the diet. The concentrations of dioxins and furans (PCDD/Fs), dioxin-like PCBs (DL-PCBs), non-dioxin-like PCBs (NDL-PCBs, PCB 6 ) and polybrominated flame retardants (PBDEs) were determined in the liver of 784 individual Northeast Arctic cod caught at 32 positions in the Barents Sea in the period from 2009–2010. In addition, muscle samples from 30 individual cod were analysed for the same substances. The mean concentration of the sum of PCDD/Fs and DL-PCBs for all samples was 14.2 ng TEQ who-2005 /kg ww with a variation between 1.0 and 151 ng TEQ/kg ww. The concentrations of POPs in the fillet samples were very low

  13. Dopamine Gene Profiling to Predict Impulse Control and Effects of Dopamine Agonist Ropinirole.

    Science.gov (United States)

    MacDonald, Hayley J; Stinear, Cathy M; Ren, April; Coxon, James P; Kao, Justin; Macdonald, Lorraine; Snow, Barry; Cramer, Steven C; Byblow, Winston D

    2016-07-01

    Dopamine agonists can impair inhibitory control and cause impulse control disorders for those with Parkinson disease (PD), although mechanistically this is not well understood. In this study, we hypothesized that the extent of such drug effects on impulse control is related to specific dopamine gene polymorphisms. This double-blind, placebo-controlled study aimed to examine the effect of single doses of 0.5 and 1.0 mg of the dopamine agonist ropinirole on impulse control in healthy adults of typical age for PD onset. Impulse control was measured by stop signal RT on a response inhibition task and by an index of impulsive decision-making on the Balloon Analogue Risk Task. A dopamine genetic risk score quantified basal dopamine neurotransmission from the influence of five genes: catechol-O-methyltransferase, dopamine transporter, and those encoding receptors D1, D2, and D3. With placebo, impulse control was better for the high versus low genetic risk score groups. Ropinirole modulated impulse control in a manner dependent on genetic risk score. For the lower score group, both doses improved response inhibition (decreased stop signal RT) whereas the lower dose reduced impulsiveness in decision-making. Conversely, the higher score group showed a trend for worsened response inhibition on the lower dose whereas both doses increased impulsiveness in decision-making. The implications of the present findings are that genotyping can be used to predict impulse control and whether it will improve or worsen with the administration of dopamine agonists.

  14. Peripheral Dopamine in Restless Legs Syndrome

    Directory of Open Access Journals (Sweden)

    Ulrike H. Mitchell

    2018-03-01

    Full Text Available Objective/BackgroundRestless Legs Syndrome (RLS is a dopamine-dependent disorder characterized by a strong urge to move. The objective of this study was to evalulate blood levels of dopamine and other catecholamines and blood D2-subtype dopamine receptors (D2Rs in RLS.Patients/MethodsDopamine levels in blood samples from age-matched unmedicated RLS subjects, medicated RLS subjects and Controls were evaluated with high performance liquid chromatography and dopamine D2R white blood cell (WBC expression levels were determined with fluorescence-activated cell sorting and immunocytochemistry.ResultsBlood plasma dopamine levels, but not norepinepherine or epinephrine levels, were significantly increased in medicated RLS subjects vs unmedicated RLS subjects and Controls. The percentage of lymphocytes and monocytes expressing D2Rs differed between Control, RLS medicated and RLS unmedicated subjects. Total D2R expression in lymphocytes, but not monocytes, differed between Control, RLS medicated and RLS unmedicated subjects. D2Rs in lymphocytes, but not monocytes, were sensitive to dopamine in Controls only.ConclusionDownregulation of WBCs D2Rs occurs in RLS. This downregulation is not reversed by medication, although commonly used RLS medications increase plasma dopamine levels. The insensitivity of monocytes to dopamine levels, but their downregulation in RLS, may reflect their utility as a biomarker for RLS and perhaps brain dopamine homeostasis.

  15. Monitoring OH-PCBs in PCB transport worker's urine as a non-invasive exposure assessment tool.

    Science.gov (United States)

    Haga, Yuki; Suzuki, Motoharu; Matsumura, Chisato; Okuno, Toshihiro; Tsurukawa, Masahiro; Fujimori, Kazuo; Kannan, Narayanan; Weber, Roland; Nakano, Takeshi

    2018-04-14

    In this study, we analyzed hydroxylated polychlorinated biphenyls (OH-PCBs) in urine of both PCB transport workers and PCB researchers. A method to monitor OH-PCB in urine was developed. Urine was solid-phase extracted with 0.1% ammonia/ methanol (v/v) and glucuronic acid/sulfate conjugates and then decomposed using β-glucuronidase/arylsulfatase. After alkaline digestion/derivatization, the concentration of OH-PCBs was determined by HRGC/HRMS-SIM. In the first sampling campaign, the worker's OH-PCB levels increased several fold after the PCB waste transportation work, indicating exposure to PCBs. The concentration of OH-PCBs in PCB transport workers' urine (0.55~11 μg/g creatinine (Cre)) was higher than in PCB researchers' urine (PCB storage area. In the second sampling, after recommended PCB exposure reduction measures had been enacted, the worker's PCB levels did not increase during handling of PCB equipment. This suggests that applied safety measures improved the situation. Hydroxylated trichlorobiphenyls (OH-TrCBs) were identified as a major homolog of OH-PCBs in urine. Also, hydroxylated tetrachlorobiphenyls (OH-TeCBs) to hydroxylated hexachlorobiphenyls (OH-HxCBs) were detected. For the sum of ten selected major indicators, a strong correlation to total OH-PCBs were found and these can possibly be used as non-invasive biomarkers of PCB exposure in workers managing PCB capacitors and transformer oils. We suggest that monitoring of OH-PCBs in PCB management projects could be considered a non-invasive way to detect exposure. It could also be used as a tool to assess and improve PCB management. This is highly relevant considering the fact that in the next 10 years, approx. 14 million tons of PCB waste need to be managed. Also, the selected populations could be screened to assess whether exposure at work, school, or home has taken place.

  16. Presence and function of dopamine transporter (DAT in stallion sperm: dopamine modulates sperm motility and acrosomal integrity.

    Directory of Open Access Journals (Sweden)

    Javier A Urra

    Full Text Available Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT, serotonin (SERT and norepinephrine (NET transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylaminostyryl]-N-methylpyridinium iodide (ASP(+, as substrate. In addition, we also showed that dopamine (1 mM treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909 and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility.

  17. Passive air monitoring of PCBs and PCNs across East Asia: a comprehensive congener evaluation for source characterization.

    Science.gov (United States)

    Hogarh, Jonathan Nartey; Seike, Nobuyasu; Kobara, Yuso; Habib, Ahsan; Nam, Jae-Jak; Lee, Jong-Sik; Li, Qilu; Liu, Xiang; Li, Jun; Zhang, Gan; Masunaga, Shigeki

    2012-02-01

    A comprehensive congener specific evaluation of polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) in the atmosphere was conducted across East Asia in spring 2008, applying polyurethane foam (PUF) disk passive air sampler (PAS) as monitoring device. Mean concentrations derived for Japan, China and Korea were 184 ± 24, 1100 ± 118, and 156 ± 20 pg m(-3) for ∑(202) PCBs, and 9.5 ± 1.5, 61 ± 6, and 16 ± 2.4 pg m(-3) for ∑(63) PCNs, respectively. Relative to reported data from 2004, the present results suggest that air PCBs concentrations have not changed much in Japan and Korea, while it has increased by one order of magnitude in China. From principal component analysis, combustion emerged highly culpable in contemporary emissions of both PCBs and PCNs across the East Asian sub-region. Another factor derived as important to air PCBs was re-emissions/volatilization. Signals from PCBs formulations were also picked, but their general importance was virtually consigned to the re-emissions/volatilization tendencies. On the contrary, counterpart PCNs formulations did not appear to contribute much to air PCNs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra

    Directory of Open Access Journals (Sweden)

    Purves-Tyson Tertia D

    2012-08-01

    conversion of T to DHT and increasing AR mRNA. Further, testosterone may increase local dopamine synthesis and metabolism, thereby changing dopamine regulation within the substantia nigra. We show that testosterone action through both AR and ERs modulates synthesis of sex steroid receptor by altering AR and ER mRNA levels in normal adolescent male substantia nigra. Increased sex steroids in the brain at adolescence may alter substantia nigra dopamine pathways, increasing vulnerability for the development of psychopathology.

  19. Exchange of polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) between air and a mixed pasture sward.

    Science.gov (United States)

    Barber, Jonathan L; Thomas, Gareth O; Bailey, Rebekah; Kerstiens, Gerhard; Jones, Kevin C

    2004-07-15

    To improve understanding of air-to-vegetation transfer of persistent organic pollutants (POPs), uptake and depuration of polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) between grass sward and air was investigated. Pasture swards were placed in fanned (2 m s(-1) wind speed) and unfanned conditions for a period of 20 days and sampled at intervals. Depuration was carried out after a short (4 days) and a long (14 days) exposure period. Prior to contamination, a mixed pasture sward at a semi-rural location contained sigmaPCN concentrations 15-20% of the sigmaPCB concentration. Uptake of both PCBs and PCNs was broadly linear in fanned and unfanned conditions over the 20-day period, i.e., the pasture did not reach equilibrium with the air. Uptake rates (fluxes) were greater under the fanned conditions. The difference in uptake rates between fanned and unfanned conditions increased with degree of chlorination for both PCBs and PCNs, ranging between a factor of 2 for tri-chlorinated PCBs and PCNs and a factor 5 for octa-chlorinated PCBs. Depuration results over the first hours were very scattered, showing an initial period of loss, followed by an increase in concentrations, possibly as a result of re-volatilization of PCBs from the soil in the trays, with consequent recapture by the overlying sward. Rapid clearance was observed over the following days, but depuration of PCBs and PCNs was still incomplete after 14 days, with 20% of the initial concentration of the sigmaPCBs and 10% of the sigmaPCNs retained by the sward. There was no difference in the proportion of POPs retained in the sward between the 4- and 14-day contamination treatments. POP-specific differences in the amount of compound "trapped" in leaves after contamination were observed. The results show that, although changes in the rate of air movement around a pasture have an effect on the uptake rate of POPs into the vegetation, plant-side resistance controls both the air-to-pasture and

  20. Human dietary exposure and levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCBs) and non-dioxin-like polychlorinated biphenyls (NDL-PCBs) in free-range eggs close to a secondary aluminum smelter, Northern Italy

    International Nuclear Information System (INIS)

    Squadrone, S.; Brizio, P.; Nespoli, R.; Stella, C.; Abete, M.C.

    2015-01-01

    PCDD/Fs and PCBs are environmentally persistent substances that have been associated with adverse effects on human health. Contamination of soils, animal feed and pastures leads to their bioaccumulation of in food products of animal origin, which are considered the major source of intake of these contaminants in humans. We analyzed eggs from free-range hens, sampled from small farms, located within a distance of 4.5 km from a secondary aluminum smelter in Northern Italy. The concentrations of PCDD/Fs, DL-PCBs and NDL-PCBs were higher in eggs from locations close to the plant, and strongly exceeded the limits set by EU Regulation 1259/2011 (2.5 pg WHO TEQ fat g"−"1 for PCDD/Fs, 5.0 pg WHO TEQ g"−"1 for PCDD/Fs and DL-PCBs L, 40 ng g"−"1 for NDL-PCBs). Consuming contaminated eggs may pose a risk for human health, especially for children (≤9 years) and infants (≤3 years), due to the 2-fold excess of the current exposure limits. - Highlights: • We analyzed free-range eggs from farms close to a secondary aluminum smelter (ALS). • Concentrations of dioxins and PCBs strongly exceeded the limit set by EU Regulation. • Concentrations decrease at increasing distances from the plant. • Consuming contaminated eggs may pose a health risk for humans. - Concentrations of PCDD/Fs, DL-PCBs and NDL-PCBs are of concern in free-range eggs close to a secondary aluminum smelter.

  1. Potential for phytoextraction of PCBs from contaminated soils using weeds.

    Science.gov (United States)

    Ficko, Sarah A; Rutter, Allison; Zeeb, Barbara A

    2010-07-15

    A comprehensive investigation of the potential of twenty-seven different species of weeds to phytoextract polychlorinated biphenyls (PCBs) from contaminated soil was conducted at two field sites (Etobicoke and Lindsay) in southern Ontario, Canada. Soil concentrations were 31 microg/g and 4.7 microg/g at each site respectively. All species accumulated PCBs in their root and shoot tissues. Mean shoot concentrations at the two sites ranged from 0.42 microg/g for Chenopodium album to 35 microg/g for Vicia cracca (dry weight). Bioaccumulation factors (BAF=[PCB](plant tissue)/[PCB](mean soil)) at the two sites ranged from 0.08 for Cirsium vulgare to 1.1 for V. cracca. Maximum shoot extractions were 420 microg for Solidago canadensis at the Etobicoke site, and 120 microg for Chrysanthemum leucanthemum at the Lindsay site. When plant density was taken into account with a theoretical density value, seventeen species appeared to be able to extract a similar or greater quantity of PCBs into the shoot tissue than pumpkins (Curcurbita pepo ssp. pepo) which are known PCB accumulators. Therefore, some of these weed species are promising candidates for future phytoremediation studies. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  2. Levels, distribution and air-soil exchange fluxes of polychlorinated biphenyls (PCBs) in the environment of Punjab Province, Pakistan.

    Science.gov (United States)

    Syed, Jabir Hussain; Malik, Riffat Naseem; Li, Jun; Zhang, Gan; Jones, Kevin C

    2013-11-01

    An initial survey of the concentrations of polychlorinated biphenyl (PCB) compounds in air and soils across industrial and agricultural areas of Punjab Province, Pakistan, was conducted from January to March 2011. The total concentration of all PCBs (31 PCBs) ranged from 34 to 389pgm(-3) in air and from 7 to 45ngg(-1) dry weight in soils, where both ranges were similar to the average ranges in other areas of the world. PCBs were elevated across industrial regions near urban and industrial sources. Consistently low air concentrations of PCBs at the agricultural sites suggest that they are less widespread or uniformly distributed in the Pakistani atmosphere. The calculated air and soil fugacity fraction values indicated that soils are a potential secondary source of PCBs in agricultural areas, whereas they are in equilibrium or atmospheric deposition in industrial and urban areas. TEQ concentrations of dioxin-like PCBs for soil samples met the Canadian standard. However, local authorities should address the human health threats from urban and industrial soils in Punjab Province, Pakistan. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. 40 CFR 761.187 - Reporting importers and by persons generating PCBs in excluded manufacturing processes.

    Science.gov (United States)

    2010-07-01

    ...) MANUFACTURING, PROCESSING, DISTRIBUTION IN COMMERCE, AND USE PROHIBITIONS General Records and Reports § 761.187 Reporting importers and by persons generating PCBs in excluded manufacturing processes. In addition to... generating PCBs in excluded manufacturing processes. 761.187 Section 761.187 Protection of Environment...

  4. Alterations in brain extracellular dopamine and glycine levels following combined administration of the glycine transporter type-1 inhibitor Org-24461 and risperidone.

    Science.gov (United States)

    Nagy, Katalin; Marko, Bernadett; Zsilla, Gabriella; Matyus, Peter; Pallagi, Katalin; Szabo, Geza; Juranyi, Zsolt; Barkoczy, Jozsef; Levay, Gyorgy; Harsing, Laszlo G

    2010-12-01

    The most dominant hypotheses for the pathogenesis of schizophrenia have focused primarily upon hyperfunctional dopaminergic and hypofunctional glutamatergic neurotransmission in the central nervous system. The therapeutic efficacy of all atypical antipsychotics is explained in part by antagonism of the dopaminergic neurotransmission, mainly by blockade of D(2) dopamine receptors. N-methyl-D-aspartate (NMDA) receptor hypofunction in schizophrenia can be reversed by glycine transporter type-1 (GlyT-1) inhibitors, which regulate glycine concentrations at the vicinity of NMDA receptors. Combined drug administration with D(2) dopamine receptor blockade and activation of hypofunctional NMDA receptors may be needed for a more effective treatment of positive and negative symptoms and the accompanied cognitive deficit in schizophrenia. To investigate this type of combined drug administration, rats were treated with the atypical antipsychotic risperidone together with the GlyT-1 inhibitor Org-24461. Brain microdialysis was applied in the striatum of conscious rats and determinations of extracellular dopamine, DOPAC, HVA, glycine, glutamate, and serine concentrations were carried out using HPLC/electrochemistry. Risperidone increased extracellular concentrations of dopamine but failed to influence those of glycine or glutamate measured in microdialysis samples. Org-24461 injection reduced extracellular dopamine concentrations and elevated extracellular glycine levels but the concentrations of serine and glutamate were not changed. When risperidone and Org-24461 were added in combination, a decrease in extracellular dopamine concentrations was accompanied with sustained elevation of extracellular glycine levels. Interestingly, the extracellular concentrations of glutamate were also enhanced. Our data indicate that coadministration of an antipsychotic with a GlyT-1 inhibitor may normalize hypofunctional NMDA receptor-mediated glutamatergic neurotransmission with reduced

  5. Bioaccumulation dynamics of polychlorinated biphenyls (PCBs) and organochlorine pesticides

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Bioaccumulation dynamics of polychlorinated biphenyls (PCBs) and organochlorine pesticides was examined in young-of-the-year bluefish from seven sub-estuaries of New...

  6. NEUROTRANSMITTERS AND IMMUNITY: 1. DOPAMINE

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2007-08-01

    Full Text Available Dopamine is one of the principal neurotransmitters in the central nervous system (CNC, and its neuronal pathways are involved in several key functions such as behavior (Hefco et al., 2003a,b, control of movement, endocrine regulation, immune response (Fiserova et al., 2002; Levite et al., 2001, Hritcu et al., 2006a,b,c, and cardiovascular function. Dopamine has at least five G-protein, coupled receptor subtypes, D1-D5, each arising from a different gene (Sibley et al., 1993. Traditionally, these receptors have been classified into D1-like (the D1 and D5 and D2-like (D2, D3 and D4 receptors subtypes, primarily according to their ability to stimulate or inhibit adenylate cyclase, respectively, and to their pharmacological characteristics (Seeman et al., 1993. Receptors for dopamine (particularly of D2 subclass are the primary therapeutic target in a number of neuropathological disorders including schizophrenia, Parkinson’s disease and Huntington’s chorea (Seeman et al., 1987. Neither dopamine by itself, nor dopaminergic agonists by themselves, has been shown to activate T cell function. Nevertheless, lymphocytes are most probably exposed to dopamine since the primary and secondary lymphoid organs of various mammals are markedly innervated, and contain nerve fibers which stain for tyrosine hydroxylase (Weihe et al., 1991, the enzyme responsible for dopamine synthesis. Moreover, cathecolamines and their metabolites are present in single lymphocytes and in extracts of T and B cell clones, and pharmacological inhibition of tyrosine hydroxylase reduces catecholamine levels, suggesting catecholamine synthesis by lymphocytes (Bergquist et al., 1994. The existence of putative dopamine receptors of D2, D3, D4 and D5 subtypes on immune cells has been proposed of several authors, primarily on the basis of dopaminergic ligand binding assays and specific mRNA expression as monitored by reverse transcription-PCR. Several experiments evoked the idea of a

  7. Gaseous and Freely-Dissolved PCBs in the Lower Great Lakes Based on Passive Sampling: Spatial Trends and Air-Water Exchange.

    Science.gov (United States)

    Liu, Ying; Wang, Siyao; McDonough, Carrie A; Khairy, Mohammed; Muir, Derek C G; Helm, Paul A; Lohmann, Rainer

    2016-05-17

    Polyethylene passive sampling was performed to quantify gaseous and freely dissolved polychlorinated biphenyls (PCBs) in the air and water of Lakes Erie and Ontario during 2011-2012. In view of differing physical characteristics and the impacts of historical contamination by PCBs within these lakes, spatial variation of PCB concentrations and air-water exchange across these lakes may be expected. Both lakes displayed statistically similar aqueous and atmospheric PCB concentrations. Total aqueous concentrations of 29 PCBs ranged from 1.5 pg L(-1) in the open lake of Lake Erie (site E02) in 2011 spring to 105 pg L(-1) in Niagara (site On05) in 2012 summer, while total atmospheric concentrations were 7.7-634 pg m(-3) across both lakes. A west-to-east gradient was observed for aqueous PCBs in Lake Erie. River discharge and localized influences (e.g., sediment resuspension and regional alongshore transport) likely dominated spatial trends of aqueous PCBs in both lakes. Air-water exchange fluxes of Σ7PCBs ranged from -2.4 (±1.9) ng m(-2) day(-1) (deposition) in Sheffield (site E03) to 9.0 (±3.1) ng m(-2) day(-1) (volatilization) in Niagara (site On05). Net volatilization of PCBs was the primary trend across most sites and periods. Almost half of variation in air-water exchange fluxes was attributed to the difference in aqueous concentrations of PCBs. Uncertainty analysis in fugacity ratios and mass fluxes in air-water exchange of PCBs indicated that PCBs have reached or approached equilibrium only at the eastern Lake Erie and along the Canadian shore of Lake Ontario sites, where air-water exchange fluxes dominated atmospheric concentrations.

  8. Decomposition of PCBs in transformer oil using an electron beam accelerator

    Science.gov (United States)

    Jung, In-Ha; Lee, Myun-Joo; Mah, Yoon-Jung

    2012-07-01

    Decomposition of PCBs in commercially used transformer oil used for more than 30 years has been carried out at normal temperature and pressure without any additives using an electron beam accelerator. The experiments were carried out in two ways: batch and continuous pilot plant with 1.5 MeV of energy, a 50 mA current, and 75 kW of power in a commercial scale accelerator. The electron beam irradiation seemed to transform large molecular weight compounds into lower ones, but the impact was considered too small on the physical properties of oil. Residual concentrations of PCBs after irradiation depend on the absorption dose of the electron beam energy, but aliphatic chloride compounds were produced at higher doses of irradiation. As the results from FT-NMR, chloride ions decomposed from the PCBs are likely to react with aliphatic hydro carbon compounds rather than existing as free radical ions in the transformer oil. Since this is a dry process, treated oil can be used as cutting oil or machine oil for heavy equipment without any additional treatments.

  9. De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder.

    Science.gov (United States)

    Hamilton, P J; Campbell, N G; Sharma, S; Erreger, K; Herborg Hansen, F; Saunders, C; Belovich, A N; Sahai, M A; Cook, E H; Gether, U; McHaourab, H S; Matthies, H J G; Sutcliffe, J S; Galli, A

    2013-12-01

    De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.

  10. Cross-hemispheric dopamine projections have functional significance

    Science.gov (United States)

    Fox, Megan E.; Mikhailova, Maria A.; Bass, Caroline E.; Takmakov, Pavel; Gainetdinov, Raul R.; Budygin, Evgeny A.; Wightman, R. Mark

    2016-01-01

    Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson’s disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine–lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres. PMID:27298371

  11. Tyrosine hydroxylase immunoreactivity and [3H]WIN 35,428 binding to the dopamine transporter in a hamster model of idiopathic paroxysmal dystonia

    International Nuclear Information System (INIS)

    Nobrega, J.N.; Gernert, M.; Loescher, W.; Raymond, R.; Belej, T.; Richter, A.

    1999-01-01

    Recent pharmacological studies and receptor analyses have suggested that dopamine neurotransmission is enhanced in mutant dystonic hamsters (dt sz ), a model of idiopathic paroxysmal dystonia which displays attacks of generalized dystonia in response to mild stress. In order to further characterize the nature of dopamine alterations, the present study investigated possible changes in the number of dopaminergic neurons, as defined by tyrosine hydroxylase immunohistochemistry, as well as binding to the dopamine transporter labelled with [ 3 H]WIN 35,428 in dystonic hamsters. No differences in the number of tyrosine hydroxylase-immunoreactive neurons were found within the substantia nigra and ventral tegmental area of mutant hamsters compared to non-dystonic control hamsters. Similarly, under basal conditions, i.e. in the absence of a dystonic episode, no significant changes in [ 3 H]WIN 35,428 binding were detected in dystonic brains. However, in animals killed during the expression of severe dystonia, significant decreases in dopamine transporter binding became evident in the nucleus accumbens and ventral tegmental area in comparison to controls exposed to the same external stimulation. Since stimulation tended to increase [ 3 H]WIN 35,428 binding in control brains, the observed decrease in the ventral tegmental area appeared to be due primarily to the fact that binding was increased less in dystonic brains than in similarly stimulated control animals.This finding could reflect a diminished ability of the dopamine transporter to undergo adaptive changes in response to external stressful stimulation in mutant hamsters. The selective dopamine uptake inhibitor GBR 12909 (20 mg/kg) aggravated dystonia in mutant hamsters, further suggesting that acute alterations in dopamine transporter function during stimulation may be an important component of dystonia in this model. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  12. The binding sites for cocaine and dopamine in the dopamine transporter overlap

    DEFF Research Database (Denmark)

    Beuming, Thijs; Kniazeff, Julie; Bergmann, Marianne L

    2008-01-01

    Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog Leu......T. Our models suggest that the binding site for cocaine and cocaine analogs is deeply buried between transmembrane segments 1, 3, 6 and 8, and overlaps with the binding sites for the substrates dopamine and amphetamine, as well as for benztropine-like DAT inhibitors. We validated our models by detailed...... inhibition of dopamine transport by cocaine....

  13. Blood levels of dioxins, furans, dioxin-like PCBs, and TEQs in general populations: a review, 1989-2010.

    Science.gov (United States)

    Consonni, Dario; Sindaco, Raffaella; Bertazzi, Pier Alberto

    2012-09-01

    A comprehensive worldwide literature review of blood levels of dioxins and dioxin-like compounds in non-exposed adult general populations was performed. The studies published in 1989-2010 reporting information on polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho-PCBs (nPCBs), mono-ortho-PCBs (mPCBs) levels and Toxic Equivalencies (TEQs, a summary weighted measure of their combined toxicity) were reviewed. TEQs were calculated using as standard the most recent WHO 2005 reevaluation of Toxic Equivalency Factors (TEFs). Weighted multiple regression analyses adjusted for year, subject's age, type of sample analyzed, method used for values below detection limit, and central tendency measure used were performed for each congener and standardized TEQs (log-transformed). We identified 187 studies regarding 29,687 subjects of 26 countries. Year of blood collection ranged from 1985 to 2008. The studies reporting congener levels 161. In adjusted analyses, European countries showed higher levels of most dioxin-like congeners and TEQs. A strong positive association of subjects' age with most congeners and with TEQ values was found, confirming previous findings. Significant decreases over time (1985-2008) were documented for PCCDs, PCDFs, and TEQs including their contributions. No significant decrease was found for non-ortho-PCBs, notably PCB 126. Only some mono-ortho-PCBs showed clear significant declines. Accordingly, TEQs including only PCB contribution did not decrease over time. In interpreting these findings, it should be considered that for dioxin-like PCBs the analysis period was shorter (17 years), since these compounds were first measured in 1992. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Assessment of gold and silver in assorted mobile phone printed circuit boards (PCBs): Original article.

    Science.gov (United States)

    Vats, M C; Singh, S K

    2015-11-01

    Demand for gold and silver has been escalating with increasing usage of electronic equipment globally. Around 267.3 MT of gold and 7275 MT of silver are being consumed annually for manufacturing mobile phones, laptops and other electronic equipment. However, only 15% is recuperated from these equipment; the remainder lies in the storage yards or landfills. The waste comprise glass, plastics, wires, batteries, PCBs, metal casing, etc. The PCB is composed of precious metals, which creates immense purpose for recycling and recovery. This paper characterises and assesses the recoverable metallic fraction of gold and silver from PCBs of mobile phones. The methodology is based on dismantling of the mobile handset and subjecting the PCBs to roasting and acid digestion. The digested samples were analysed by atomic absorption spectroscopy and the content of gold and silver in the PCBs was to be found in the range of 0.009-0.017% and 0.25-0.79% by weight respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Computational systems analysis of dopamine metabolism.

    Directory of Open Access Journals (Sweden)

    Zhen Qi

    2008-06-01

    Full Text Available A prominent feature of Parkinson's disease (PD is the loss of dopamine in the striatum, and many therapeutic interventions for the disease are aimed at restoring dopamine signaling. Dopamine signaling includes the synthesis, storage, release, and recycling of dopamine in the presynaptic terminal and activation of pre- and post-synaptic receptors and various downstream signaling cascades. As an aid that might facilitate our understanding of dopamine dynamics in the pathogenesis and treatment in PD, we have begun to merge currently available information and expert knowledge regarding presynaptic dopamine homeostasis into a computational model, following the guidelines of biochemical systems theory. After subjecting our model to mathematical diagnosis and analysis, we made direct comparisons between model predictions and experimental observations and found that the model exhibited a high degree of predictive capacity with respect to genetic and pharmacological changes in gene expression or function. Our results suggest potential approaches to restoring the dopamine imbalance and the associated generation of oxidative stress. While the proposed model of dopamine metabolism is preliminary, future extensions and refinements may eventually serve as an in silico platform for prescreening potential therapeutics, identifying immediate side effects, screening for biomarkers, and assessing the impact of risk factors of the disease.

  16. The role of spinal pathways in dopamine mediated alteration in the tail-flick reflex in rats

    DEFF Research Database (Denmark)

    Jensen, T S; Schrøder, H D; Smith, D F

    1984-01-01

    The latency of the tail-flick, following intrathecal infusion of the dopamine (DA) agonist, R-apomorphine was measured in rats with intact spinal cord or with spinal cord lesions. Apomorphine failed to influence the tail-flick response in intact rats, whereas it elevated the latency of the tail-f...

  17. Dopamine receptors in human gastrointestinal mucosa

    International Nuclear Information System (INIS)

    Hernandez, D.E.; Mason, G.A.; Walker, C.H.; Valenzuela, J.E.

    1987-01-01

    Dopamine is a putative enteric neurotransmitter that has been implicated in exocrine secretory and motility functions of the gastrointestinal tract of several mammalian species including man. This study was designed to determine the presence of dopamine binding sites in human gastric and duodenal mucosa and to describe certain biochemical characteristics of these enteric receptor sites. The binding assay was performed in triplicate with tissue homogenates obtained from healthy volunteers of both sexes using 3 H-dopamine as a ligand. The extent of nonspecific binding was determined in the presence of a 100-fold excess of unlabeled dopamine. Scatchard analysis performed with increasing concentrations of 3 H-dopamine (20-500 nM) revealed a single class of saturable dopamine binding sites in gastric and duodenal mucosa. The results of this report demonstrate the presence of specific dopamine receptors in human gastric and duodenal mucosa. These biochemical data suggest that molecular abnormalities of these receptor sites may be operative in the pathogenesis of important gastrointestinal disorders. 33 references, 2 figures

  18. Spatial gradients of polychlorinated biphenyls (PCBs) and organochlorine pesticides

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Spatial gradients of polychlorinated biphenyls (PCBs) and organochlorine pesticides were examined in the young-of-the-year (YOY) blueÂżsh collected in the vicinity...

  19. The Michelin Red Guide of the Brain: role of Dopamine in Goal-oriented Navigation

    Directory of Open Access Journals (Sweden)

    Aude eRetailleau

    2014-03-01

    Full Text Available Spatial learning has been recognized over the years to be under the control of the hippocampus and related temporal lobe structures. Hippocampal damage often causes severe impairments in the ability to learn and remember a location in space defined by distal visual cues. Such cognitive disabilities are found in Parkinsonian patients. We recently investigated the role of dopamine in navigation in the 6-OHDA rat, a model of Parkinson's disease (PD commonly used to investigate the pathophysiology of dopamine depletion (Retailleau et al., 2013. We demonstrated that DA is essential to spatial learning as its depletion results in spatial impairments. Our results showed that the behavioral effect of DA depletion is correlated with modification of the neural encoding of spatial features and decision making processes in hippocampus. However, the origin of these alterations in the neural processing of the spatial information needs to be clarified. It could result from a local effect: dopamine depletion disturbs directly the processing of relevant spatial information at hippocampal level. Alternatively, it could result from a more distributed network effect: dopamine depletion elsewhere in the brain (entorhinal cortex, striatum, etc… modifies the way hippocampus processes spatial information. Recent experimental evidence in rodents, demonstrated indeed, that other brain areas are involved in the acquisition of spatial information. Amongst these, the cortex - basal ganglia loop is known to be involved in reinforcement learning and has been identified as an important contributor to spatial learning. In particular, it has been shown that altered activity of the basal ganglia striatal complex can impair the ability to perform spatial learning tasks. The present review provides a glimpse of the findings obtained over the past decade that support a dialog between these two structures during spatial learning under DA control.

  20. CHANGES IN THE DNA-BINDING OF SEVERAL TRANSCRIPTION FACTORS IN THE DEVELOPING RAT CEREBELLUM BY PCBS.

    Science.gov (United States)

    PCBs are a class of persistent halogenated aromatic hydrocarbon chemical pollutants and considered as one of the major environmental contaminants resulting from intensive industrial use and inadequate disposal. In utero exposure to PCBs has been known to cause delayed neuronal de...

  1. Simultaneous elimination of cyanotoxins and PCBs via mechanical collection of cyanobacterial blooms: An application of "green-bioadsorption concept".

    Science.gov (United States)

    Chen, Wei; Jia, Yunlu; Liu, Anyue; Zhou, Qichao; Song, Lirong

    2017-07-01

    In this study, the distribution, transfer and fate of both polychlorinated biphenyls (PCBs) and cyanotoxins via phytoplankton routes were systematically investigated in two Chinese lakes. Results indicated that PCB adsorption/bioaccumulation dynamics has significantly positive correlations with the biomass of green alga and diatoms. Total lipid content of phytoplankton is the major factor that influences PCB adsorption/bioaccumulation. Cyanobacterial blooms with relatively lower lipid content could also absorb high amount of PCBs due to their high cell density in the water columns, and this process was proposed as major route for the transfer of PCBs in Chinese eutrophic freshwater. According to these findings, a novel route on fates of PCBs via phytoplankton and a green bioadsorption concept were proposed and confirmed. In the practice of mechanical collections of bloom biomass from Lake Taihu, cyanotoxin/cyanobacteria and PCBs were found to be removed simultaneously very efficiently followed this theory. Copyright © 2016. Published by Elsevier B.V.

  2. Tyrosine hydroxylase immunoreactivity and [{sup 3}H]WIN 35,428 binding to the dopamine transporter in a hamster model of idiopathic paroxysmal dystonia

    Energy Technology Data Exchange (ETDEWEB)

    Nobrega, J.N. [Neuroimaging Research Section, Clarke Institute of Psychiatry, Toronto (Canada); Gernert, M.; Loescher, W. [Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Buenteweg 17, D-30559 Hannover (Germany); Raymond, R.; Belej, T. [Neuroimaging Research Section, Clarke Institute of Psychiatry, Toronto (Canada); Richter, A. [Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Buenteweg 17, D-30559 Hannover (Germany)

    1999-08-01

    Recent pharmacological studies and receptor analyses have suggested that dopamine neurotransmission is enhanced in mutant dystonic hamsters (dt{sup sz}), a model of idiopathic paroxysmal dystonia which displays attacks of generalized dystonia in response to mild stress. In order to further characterize the nature of dopamine alterations, the present study investigated possible changes in the number of dopaminergic neurons, as defined by tyrosine hydroxylase immunohistochemistry, as well as binding to the dopamine transporter labelled with [{sup 3}H]WIN 35,428 in dystonic hamsters. No differences in the number of tyrosine hydroxylase-immunoreactive neurons were found within the substantia nigra and ventral tegmental area of mutant hamsters compared to non-dystonic control hamsters. Similarly, under basal conditions, i.e. in the absence of a dystonic episode, no significant changes in [{sup 3}H]WIN 35,428 binding were detected in dystonic brains. However, in animals killed during the expression of severe dystonia, significant decreases in dopamine transporter binding became evident in the nucleus accumbens and ventral tegmental area in comparison to controls exposed to the same external stimulation. Since stimulation tended to increase [{sup 3}H]WIN 35,428 binding in control brains, the observed decrease in the ventral tegmental area appeared to be due primarily to the fact that binding was increased less in dystonic brains than in similarly stimulated control animals.This finding could reflect a diminished ability of the dopamine transporter to undergo adaptive changes in response to external stressful stimulation in mutant hamsters. The selective dopamine uptake inhibitor GBR 12909 (20 mg/kg) aggravated dystonia in mutant hamsters, further suggesting that acute alterations in dopamine transporter function during stimulation may be an important component of dystonia in this model. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved000.

  3. Dopamine precursor depletion impairs structure and efficiency of resting state brain functional networks.

    Science.gov (United States)

    Carbonell, Felix; Nagano-Saito, Atsuko; Leyton, Marco; Cisek, Paul; Benkelfat, Chawki; He, Yong; Dagher, Alain

    2014-09-01

    Spatial patterns of functional connectivity derived from resting brain activity may be used to elucidate the topological properties of brain networks. Such networks are amenable to study using graph theory, which shows that they possess small world properties and can be used to differentiate healthy subjects and patient populations. Of particular interest is the possibility that some of these differences are related to alterations in the dopamine system. To investigate the role of dopamine in the topological organization of brain networks at rest, we tested the effects of reducing dopamine synthesis in 13 healthy subjects undergoing functional magnetic resonance imaging. All subjects were scanned twice, in a resting state, following ingestion of one of two amino acid drinks in a randomized, double-blind manner. One drink was a nutritionally balanced amino acid mixture, and the other was tyrosine and phenylalanine deficient. Functional connectivity between 90 cortical and subcortical regions was estimated for each individual subject under each dopaminergic condition. The lowered dopamine state caused the following network changes: reduced global and local efficiency of the whole brain network, reduced regional efficiency in limbic areas, reduced modularity of brain networks, and greater connection between the normally anti-correlated task-positive and default-mode networks. We conclude that dopamine plays a role in maintaining the efficient small-world properties and high modularity of functional brain networks, and in segregating the task-positive and default-mode networks. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

    Science.gov (United States)

    Gross, Noah B; Duncker, Patrick C; Marshall, John F

    2011-11-01

    Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

  5. α2A- and α2C-Adrenoceptors as Potential Targets for Dopamine and Dopamine Receptor Ligands.

    Science.gov (United States)

    Sánchez-Soto, Marta; Casadó-Anguera, Verònica; Yano, Hideaki; Bender, Brian Joseph; Cai, Ning-Sheng; Moreno, Estefanía; Canela, Enric I; Cortés, Antoni; Meiler, Jens; Casadó, Vicent; Ferré, Sergi

    2018-03-18

    The poor norepinephrine innervation and high density of Gi/o-coupled α 2A - and α 2C -adrenoceptors in the striatum and the dense striatal dopamine innervation have prompted the possibility that dopamine could be an effective adrenoceptor ligand. Nevertheless, the reported adrenoceptor agonistic properties of dopamine are still inconclusive. In this study, we analyzed the binding of norepinephrine, dopamine, and several compounds reported as selective dopamine D 2 -like receptor ligands, such as the D 3 receptor agonist 7-OH-PIPAT and the D 4 receptor agonist RO-105824, to α 2 -adrenoceptors in cortical and striatal tissue, which express α 2A -adrenoceptors and both α 2A - and α 2C -adrenoceptors, respectively. The affinity of dopamine for α 2 -adrenoceptors was found to be similar to that for D 1 -like and D 2 -like receptors. Moreover, the exogenous dopamine receptor ligands also showed high affinity for α 2A - and α 2C -adrenoceptors. Their ability to activate Gi/o proteins through α 2A - and α 2C -adrenoceptors was also analyzed in transfected cells with bioluminescent resonance energy transfer techniques. The relative ligand potencies and efficacies were dependent on the Gi/o protein subtype. Furthermore, dopamine binding to α 2 -adrenoceptors was functional, inducing changes in dynamic mass redistribution, adenylyl cyclase activity, and ERK1/2 phosphorylation. Binding events were further studied with computer modeling of ligand docking. Docking of dopamine at α 2A - and α 2C -adrenoceptors was nearly identical to its binding to the crystallized D 3 receptor. Therefore, we provide conclusive evidence that α 2A - and α 2C -adrenoceptors are functional receptors for norepinephrine, dopamine, and other previously assumed selective D 2 -like receptor ligands, which calls for revisiting previous studies with those ligands.

  6. Photochemical degradation of PCBs in snow.

    Science.gov (United States)

    Matykiewiczová, Nina; Klánová, Jana; Klán, Petr

    2007-12-15

    This work represents the first laboratory study known to the authors describing photochemical behavior of persistent organic pollutants in snow at environmentally relevant concentrations. The snow samples were prepared by shock freezing of the corresponding aqueous solutions in liquid nitrogen and were UV-irradiated in a photochemical cold chamber reactor at -25 degrees C, in which simultaneous monitoring of snow-air exchange processeswas also possible. The main photodegradation pathway of two model snow contaminants, PCB-7 and PCB-153 (c approximately 100 ng kg(-1)), was found to be reductive dehalogenation. Possible involvement of the water molecules of snow in this reaction has been excluded by performing the photolyses in D2O snow. Instead, trace amounts of volatile organic compounds have been proposed to be the major source of hydrogen atom in the reduction, and this hypothesis was confirmed by the experiments with deuterated organic cocontaminants, such as d6-ethanol or d8-tetrahydrofuran. It is argued that bimolecular photoreduction of PCBs was more efficient or feasible than any other phototransformations under the experimental conditions used, including the coupling reactions. The photodegradation of PCBs, however, competed with a desorption process responsible for the pollutant loss from the snow samples, especially in case of lower molecular-mass congeners. Organic compounds, apparently largely located or photoproduced on the surface of snow crystals, had a predisposition to be released to the air but, at the same time, to react with other species in the gas phase. It is concluded that physicochemical properties of the contaminants and trace co-contaminants, their location and local concentrations in the matrix, and the wavelength and intensity of radiation are the most important factors in the evaluation of organic contaminants' lifetime in snow. Based on the results, it has been estimated that the average lifetime of PCBs in surface snow, connected

  7. [123I]Epidepride neuroimaging of dopamine D2/D3 receptor in chronic MK-801-induced rat schizophrenia model

    International Nuclear Information System (INIS)

    Huang, Yuan-Ruei; Shih, Jun-Ming; Chang, Kang-Wei; Huang, Chieh; Wu, Yu-Lung; Chen, Chia-Chieh

    2012-01-01

    Purpose: [ 123 I]Epidepride is a radio-tracer with very high affinity for dopamine D 2 /D 3 receptors in brain. The importance of alteration in dopamine D 2 /D 3 receptor binding condition has been wildly verified in schizophrenia. In the present study we set up a rat schizophrenia model by chronic injection of a non-competitive NMDA receptor antagonist, MK-801, to examine if [ 123 I]epidepride could be used to evaluate the alterations of dopamine D 2 /D 3 receptor binding condition in specific brain regions. Method: Rats were given repeated injection of MK-801 (dissolved in saline, 0.3 mg/kg) or saline for 1 month. Afterwards, total distance traveled (cm) and social interaction changes were recorded. Radiochemical purity of [ 123 I]epidepride was analyzed by Radio-Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [ 123 I]epidepride neuroimages were obtained by ex vivo autoradiography and small animal SPECT/CT. Data obtained were then analyzed to determine the changes of specific binding ratio. Result: Chronic MK-801 treatment for a month caused significantly increased local motor activity and induced an inhibition of social interaction. As shown in [ 123 I]epidepride ex vivo autoradiographs, MK-801 induced a decrease of specific binding ratio in the striatum (24.01%), hypothalamus (35.43%), midbrain (41.73%) and substantia nigra (37.93%). In addition, [ 123 I]epidepride small animal SPECT/CT neuroimaging was performed in the striatum and midbrain. There were statistically significant decreases in specific binding ratio in both the striatum (P 123 I]epidepride is a useful radio-tracer to reveal the alterations of dopamine D 2 /D 3 receptor binding in a rat schizophrenia model and is also helpful to evaluate therapeutic effects of schizophrenia in the future.

  8. Evaluation of PCB sources and releases for identifying priorities to reduce PCBs in Washington State (USA).

    Science.gov (United States)

    Davies, Holly; Delistraty, Damon

    2016-02-01

    Polychlorinated biphenyls (PCBs) are ubiquitously distributed in the environment and produce multiple adverse effects in humans and wildlife. As a result, the purpose of our study was to characterize PCB sources in anthropogenic materials and releases to the environment in Washington State (USA) in order to formulate recommendations to reduce PCB exposures. Methods included review of relevant publications (e.g., open literature, industry studies and reports, federal and state government databases), scaling of PCB sources from national or county estimates to state estimates, and communication with industry associations and private and public utilities. Recognizing high associated uncertainty due to incomplete data, we strived to provide central tendency estimates for PCB sources. In terms of mass (high to low), PCB sources include lamp ballasts, caulk, small capacitors, large capacitors, and transformers. For perspective, these sources (200,000-500,000 kg) overwhelm PCBs estimated to reside in the Puget Sound ecosystem (1500 kg). Annual releases of PCBs to the environment (high to low) are attributed to lamp ballasts (400-1500 kg), inadvertent generation by industrial processes (900 kg), caulk (160 kg), small capacitors (3-150 kg), large capacitors (10-80 kg), pigments and dyes (0.02-31 kg), and transformers (PCB distribution and decrease exposures include assessment of PCBs in buildings (e.g., schools) and replacement of these materials, development of Best Management Practices (BMPs) to contain PCBs, reduction of inadvertent generation of PCBs in consumer products, expansion of environmental monitoring and public education, and research to identify specific PCB congener profiles in human tissues.

  9. Dopamine versus noradrenaline in septic shock

    Directory of Open Access Journals (Sweden)

    Bo Xu

    2011-10-01

    Full Text Available BackgroundThe ‘Surviving Sepsis’ Campaign guidelines recommend theuse of dopamine or noradrenaline as the first vasopressor inseptic shock. However, information that guides clinicians inchoosing between dopamine and noradrenaline as the firstvasopressor in patients with septic shock is limited.ObjectiveThis article presents a review of the literature regarding theuse of dopamine versus noradrenaline in patients with septicshock.ResultsTwo randomised controlled trials (RCT and two largeprospective cohort studies were analysed. RCT data showeddopamine was associated with increased arrhythmic events.One cohort study found dopamine was associated with higher30-day mortality. The other cohort study found noradrenalinewas associated with higher 28-day mortality.DiscussionData on the use of dopamine versus noradrenaline in patientswith septic shock is limited. Following the recent SOAP IIstudy, there is now strong evidence that the use of dopaminein septic shock is associated with significantly morecardiovascular adverse events, compared tonoradrenaline.ConclusionNoradrenaline should be used as the initial vasopressor inseptic shock to avoid the arrhythmic events associatedwith dopamine.

  10. Origins of altered reinforcement effects in ADHD

    Directory of Open Access Journals (Sweden)

    Tripp Gail

    2009-02-01

    Full Text Available Abstract Attention-deficit/hyperactivity disorder (ADHD, characterized by hyperactivity, impulsiveness and deficient sustained attention, is one of the most common and persistent behavioral disorders of childhood. ADHD is associated with catecholamine dysfunction. The catecholamines are important for response selection and memory formation, and dopamine in particular is important for reinforcement of successful behavior. The convergence of dopaminergic mesolimbic and glutamatergic corticostriatal synapses upon individual neostriatal neurons provides a favorable substrate for a three-factor synaptic modification rule underlying acquisition of associations between stimuli in a particular context, responses, and reinforcers. The change in associative strength as a function of delay between key stimuli or responses, and reinforcement, is known as the delay of reinforcement gradient. The gradient is altered by vicissitudes of attention, intrusions of irrelevant events, lapses of memory, and fluctuations in dopamine function. Theoretical and experimental analyses of these moderating factors will help to determine just how reinforcement processes are altered in ADHD. Such analyses can only help to improve treatment strategies for ADHD.

  11. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration

    Directory of Open Access Journals (Sweden)

    Caroline E Bass

    2013-11-01

    Full Text Available There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2 on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.

  12. LOW DOPAMINE D2 RECEPTOR INCREASES VULNERABILITY TO OBESITY VIA REDUCED PHYSICAL ACTIVITY NOT INCREASED APPETITIVE MOTIVATION

    Science.gov (United States)

    Beeler, Jeff A.; Faust, Rudolf P.; Turkson, Susie; Ye, Honggang; Zhuang, Xiaoxi

    2015-01-01

    Background The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a “reward deficiency” and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. Methods We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. Results The KD mice did not gain more weight or show increased appetitive motivation compared to wild-type (WT) in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than WT, obtaining no protective benefit from exercise opportunities. Conclusions These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating. PMID:26281715

  13. Organochlorine Pesticides And Pcbs In Human Breast Milk ...

    African Journals Online (AJOL)

    One hundred and Fifty (150) samples of human breast milk (colostrums) collected from donors patronizing a postnatal center in Nigeria were analyzed for the levels of lindane, total DDT and total PCBs residues. Donors were stratified with respect to factors that may affect accumulation of these compounds such as age, ...

  14. Organochlorine Pesticides (OCs) and Polychlorinated Biphenyls (PCBs) in Tilapia zillii from Lake El-Manzala, Egypt

    International Nuclear Information System (INIS)

    El-Greisy, Zeinab Abdalbagi; Abdallah, A. Mohamed Ali

    2005-01-01

    A fresh water fish species, (Tilapia zillii) from Lake El-Manzala was analyzed for concentrations of several Organochlorine pesticides (OCs) and Polychlorine piphenyl's (PCBs) in liver, gonads, mesenteric fat, flesh and the digestive tract in mature fish during the breeding season. Polychlorinated piphenyls (PCBs) and Organochloripe pesticides (OCs) were calculated in (ng/g) dry weight (dw) in homogenized samples. The obtained results revealed differences in lipid content between these different organs. The females showed higher lipid content than males. There was significant positive correlation the lipid content and organochlorines and polychlorinated biphenyls (PCBs). The results come concomitant with the lipophilicity of studied compounds. However, the recoded concentration of these studied pollutants still does not exceed international hazardous levels. (author)

  15. Generation of an activating Zn(2+) switch in the dopamine transporter

    DEFF Research Database (Denmark)

    Loland, Claus Juul; Norregaard, Lene; Litman, Thomas

    2002-01-01

    Binding of Zn(2+) to the endogenous Zn(2+) binding site in the human dopamine transporter leads to potent inhibition of [(3)H]dopamine uptake. Here we show that mutation of an intracellular tyrosine to alanine (Y335A) converts this inhibitory Zn(2+) switch into an activating Zn(2+) switch, allowing...... Zn(2+)-dependent activation of the transporter. The tyrosine is part of a conserved YXX Phi trafficking motif (X is any residue and Phi is a residue with a bulky hydrophobic group), but Y335A did not show alterations in surface targeting or protein kinase C-mediated internalization. Despite wild...... for several substrates was increased. However, the presence of Zn(2+) in micromolar concentrations increased the V(max) up to 24-fold and partially restored the apparent affinities. The capability of Zn(2+) to restore transport is consistent with a reversible, constitutive shift in the distribution...

  16. Residues of dioxins and PCBs in fat of growing pigs and broilers fed contaminated feed

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.; Kan, C.A.; Bovee, T.F.H.; Weg, van der G.; Onstenk, C.G.M.; Traag, W.A.

    2004-01-01

    To investigate the kinetics of PCBs and dioxins, 3 week old broilers and 3 month old pigs were fed with a 10-fold diluted feed from the Belgium crisis for one week, followed by a period on clean feed. In the case of broilers this resulted in levels for dioxins, non-ortho and mono-ortho PCBs in fat

  17. Enantioselective gas chromatographic separation of methylsulfonyl PCBs in seal blubber, pelican muscle and human adipose tissues

    Energy Technology Data Exchange (ETDEWEB)

    Karasek, L.; Rosmus, J. [Veterinary Institute Prague (Czech Republic). Dept. of Chemistry; Hajslova, J. [Institute of Chemical Technology (Czech Republic). Dept. of Food Chemistry and Analysis; Huehnerfuss, H. [Hamburg Univ. (Germany). Inst. fuer Organische Chemie

    2004-09-15

    Methyl sulfone derivatives are known to represent primary metabolic products of PCBs (MeSO2- CB) and DDE (MeSO2-DDE). These metabolites are formed via mercapturic acid pathway and belong to persistent, lipophilic compounds which accumulate in the adipose, lung, liver and kidney tissues of mammals exposed to PCBs. In 1976 Jenssen and Jansson reported the identification of PCB methyl sulfones as metabolites of PCBs in Baltic grey seal blubber. Methyl sulfones are moderately polar compounds that are only slightly less hydrophobic than the parent PCBs, and their partition coefficients fulfill the requirements for bioaccumulation. The highest concentrations have been found in kidney and lung tissues of seals, otters, beluga whales, polar bears, fishes and in human tissues. In the present investigation two samples of seal blubber, two pelican muscles and eleven human adipose tissue samples were analysed with regard to their concentrations of PCB parent compounds as well as to the respective chiral methylsulfonyl metabolites.

  18. Dopamine-imprinted monolithic column for capillary electrochromatography.

    Science.gov (United States)

    Aşır, Süleyman; Sarı, Duygu; Derazshamshir, Ali; Yılmaz, Fatma; Şarkaya, Koray; Denizli, Adil

    2017-11-01

    A dopamine-imprinted monolithic column was prepared and used in capillary electrochromatography as stationary phase for the first time. Dopamine was selectively separated from aqueous solution containing the competitor molecule norepinephrine, which is similar in size and shape to the template molecule. Morphology of the dopamine-imprinted column was observed by scanning electron microscopy. The influence of the organic solvent content of mobile phase, applied pressure and pH of the mobile phase on the recognition of dopamine by the imprinted monolithic column has been evaluated, and the imprinting effect in the dopamine-imprinted monolithic polymer was verified. Developed dopamine-imprinted monolithic column resulted in excellent separation of dopamine from structurally related competitor molecule, norepinephrine. Separation was achieved in a short period of 10 min, with the electrophoretic mobility of 5.81 × 10 -5  m 2 V -1 s -1 at pH 5.0 and 500 mbar pressure. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Interaction of structural analogs of dopamine, chlorpromazine and sulpiride with striatal dopamine receptors

    International Nuclear Information System (INIS)

    Wallace, R.A.

    1987-01-01

    The objectives of these studies were to determine if the nitrogen atom of dopaminergic agonists and antagonists drugs is required for interaction with the D-1 and D-2 dopamine receptors and whether the positively charged or uncharged molecular species interacts with these receptors. To address these issues, permanently charged analogs of dopamine, chlorpromazine and sulpiride were synthesized in which a dimethylsulfonium, dimethylselenonium or quaternary ammonium group replaced the amine group. Permanently uncharged analogs which contained a methylsulfide, methylselenide and sulfoxide group instead of an amine group were also synthesized. The interactions of these compounds with striatal dopamine receptors were studied. We found that the permanently charged dopamine analogs bound to the D-2 receptor of striatal membranes like conventional dopaminergic agonists and displayed agonist activity at the D-2 receptor regulating potassium-evoked [ 3 H] acetylcholine release. In contrast, the permanently uncharged analogs bound only to the high affinity state of the D-2 receptor and had neither agonist or antagonist activity

  20. Monitoring of organic micropollutants in Ghana by combination of pellet watch with sediment analysis: E-waste as a source of PCBs

    International Nuclear Information System (INIS)

    Hosoda, Junki; Ofosu-Anim, John; Sabi, Edward Benjamin; Akita, Lailah Gifty; Onwona-Agyeman, Siaw; Yamashita, Rei; Takada, Hideshige

    2014-01-01

    Highlights: • Pellet watch was conducted in Ghanaian coast, including capital city, Accra. • PCBs concentrations in pellets near Accra were higher than global background. • Sedimentary PCBs were higher at a location down e-waste scrapyard in Accra. • Triphenylbenzene, an indicator of plastic combustion, was abundant near the dump site. • The importance of e-waste as source of PCBs in Ghana was elucidated. - Abstract: Plastic resin pellets collected at 11 beaches covering the whole Ghanaian coastline were analyzed for polychlorinated biphenyls (PCBs). PCB concentrations (∑13 congeners) were higher in Accra, capital city, and Tema (39–69 ng/g-pellets) than those in rural coastal towns (1–15 ng/g-pellets) which are close to global background, indicating local inputs of PCBs. River sediments were also analyzed for PCBs together with molecular markers. Sedimentary PCBs concentrations were highest at a site (AR02) downstream of an electronic waste (e-waste) scrapyard. At the site (AR02), concentration of linear alkylbenzenes (LABs), a marker of municipal wastewater, was lower than another site (AR03) which is located at the downstream of downtown Accra. This result suggests that PCBs are introduced more to the river from the e-waste site than from activities in downtown Accra. PAHs concentrations were relatively higher in urban areas with strong petrogenic signature. Abundance of triphenylbenzenes suggested plastic combustion near e-waste scrapyard

  1. Cancer risk assessment of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in former agricultural soils of Hong Kong

    International Nuclear Information System (INIS)

    Man, Yu Bon; Lopez, Brenda Natalia; Wang, Hong Sheng; Leung, Anna Oi Wah; Chow, Ka Lai; Wong, Ming H.

    2011-01-01

    Highlights: → Electronic recycling site contain high concentrations of PCBs and PBDEs in Hong Kong. → Changing of agricultural land use to electronic waste recycling sites can increase potential cancer risk on human. → High levels of soil organic matter in soils render PBDEs and PCBs more resistant to degradation. - Abstract: The major objective of this study was to evaluate the carcinogenic risk posed to humans through PBDEs and PCBs of changing agricultural land use for recycling of e-waste and open burning of municipal waste. Nine locations were selected to represent 6 different types of land use such as e-waste dismantling workshop (EW (DW)) and e-waste open burning site (EW (OBS)). The total concentrations for PBDEs and PCBs, and the bioaccessibility of PCBs were determined using Soxhlet extraction and in vitro simulated gastric solution, respectively. Both total and bioaccessible concentrations were subsequently used to establish the cancer risk probabilities in humans via ingestion, dermal contact and inhalation of soil particles. It was found that very low cancer risk in all 6 types of different land use was caused by BDE-209. Nevertheless, at the 95th centile, the concentration of PCBs in EW (DW) and EW (OBS) indicate a low cancer risk to humans of 40 and 2.1 in a million, respectively, while the same was also observed for the bioaccessible PCBs in EW (DW) of 1.71 ± 2.96 in a million.

  2. Residues of dioxins (PCDD/Fs) and PCBs in eggs, fat and livers of laying hens following consumption of contaminated feed

    NARCIS (Netherlands)

    Traag, W.A.; Kan, C.A.; Weg, van der G.; Onstenk, C.G.M.; Hoogenboom, L.A.P.

    2006-01-01

    Laying hens were fed with feed from the Belgian dioxin incident diluted ten-fold with non-contaminated feed, resulting in concentrations of 61 ng TEQ kg(-1) PCDD/Fs, 23 ng TEQ kg(-1) non-ortho PCBs, 116 ng TEQ kg(-1) mono-ortho PCBs and 3.2 mg kg(-1) of the seven indicator PCBs. Following exposure

  3. PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

    Science.gov (United States)

    España, Rodrigo A.; Jones, Sara R.

    2013-01-01

    The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

  4. Behavioral Modulation by Spontaneous Activity of Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    Toshiharu Ichinose

    2017-12-01

    Full Text Available Dopamine modulates a variety of animal behaviors that range from sleep and learning to courtship and aggression. Besides its well-known phasic firing to natural reward, a substantial number of dopamine neurons (DANs are known to exhibit ongoing intrinsic activity in the absence of an external stimulus. While accumulating evidence points at functional implications for these intrinsic “spontaneous activities” of DANs in cognitive processes, a causal link to behavior and its underlying mechanisms has yet to be elucidated. Recent physiological studies in the model organism Drosophila melanogaster have uncovered that DANs in the fly brain are also spontaneously active, and that this activity reflects the behavioral/internal states of the animal. Strikingly, genetic manipulation of basal DAN activity resulted in behavioral alterations in the fly, providing critical evidence that links spontaneous DAN activity to behavioral states. Furthermore, circuit-level analyses have started to reveal cellular and molecular mechanisms that mediate or regulate spontaneous DAN activity. Through reviewing recent findings in different animals with the major focus on flies, we will discuss potential roles of this physiological phenomenon in directing animal behaviors.

  5. Polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in the equatorial Indian Ocean: temporal trend, continental outflow and air-water exchange.

    Science.gov (United States)

    Huang, Yumei; Li, Jun; Xu, Yue; Xu, Weihai; Cheng, Zhineng; Liu, Junwen; Wang, Yan; Tian, Chongguo; Luo, Chunling; Zhang, Gan

    2014-03-15

    Nineteen pairs of air and seawater samples collected from the equatorial Indian Ocean onboard the Shiyan I from 4/2011 to 5/2011 were analyzed for PCBs and HCB. Gaseous concentrations of ∑(ICES)PCBs (ICES: International Council for the Exploration of the Seas) and HCB were lower than previous data over the study area. Air samples collected near the coast had higher levels of PCBs relative to those collected in the open ocean, which may be influenced by proximity to source regions and air mass origins. Dissolved concentrations of ∑(ICES)PCBs and HCB were 1.4-14 pg L⁻¹ and 0.94-13 pg L⁻¹, with the highest concentrations in the sample collected from Strait of Malacca. Fugacity fractions suggest volatilization of PCBs and HCB from the seawater to air during the cruise, with fluxes of 0.45-34 ng m⁻² d⁻¹ and 0.36-18 ng m⁻² d⁻¹, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Intranasal dopamine reduces in vivo [123I]FP-CIT binding to striatal dopamine transporter: correlation with behavioral changes and evidence for Pavlovian conditioned dopamine response

    OpenAIRE

    Maria A de Souza Silva; C. eMattern; C. eMattern; C.I. eDecheva; Joseph P. Huston; A. eSadile; M. eBeu; H.W. eMüller; Susanne eNikolaus

    2016-01-01

    Purpose: Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We ...

  7. Management of polychlorinated biphenyls (PCBs) questions ampersand answers

    International Nuclear Information System (INIS)

    1995-11-01

    This open-quotes Management of PCBs Questions and Answersclose quotes has been developed from a presentation given by Dr. John Smith of the Environmental Protection Agency (EPA), and the transcribed question and answer session which followed the presentation. Dr. Smith was featured at the first DOE complex-wide PCB Focus Group meeting held in San Francisco, California in December 1992. The meeting was attended by representatives from field elements who were actively involved in the management of PCBs. The meeting served as a forum for the exchange of information and discussion of PCB management issues. This document has been prepared as one of several guidance documents developed by the Department of Energy Office of Environmental Policy and Assistance (EH-41) (formerly the Office of Environmental Guidance, EH-23) to assist DOE elements in their PCB management programs. This document is organized into three parts: (1) an introduction describing the conception and development of this document, (2) a summary of Dr. Smith's presentation, and (3) the question and answer session

  8. Bioaccumulation of metals and PCBs in Raja clavata.

    Science.gov (United States)

    Torres, Paulo; Tristão da Cunha, Regina; Micaelo, Cristina; Rodrigues, Armindo Dos Santos

    2016-12-15

    The goal of this study was to assess stable isotopes profiles, metals concentration and PCBs in Raja clavata muscle and liver, according to sex and size, and to elucidate its suitability as a Mid-Atlantic biomonitor. The results reflected bioaccumulation and suggested biomagnification processes for As and Hg in muscle tissue. Cd, Cu and Zn were detected in high amounts in liver, Cr, Mn and Rb were relatively stable and low, Pb was not detected and Sr was present in muscle at high levels, decreasing with length. Hg and Se were strongly correlated, suggesting a mitigation role. Both tissues presented low concentrations of PCBs, especially the dioxin-like congeners, although always higher in liver and not correlated with size. None of these contaminants exceed EU legislated limits. However, they need to be monitored given study area's location, volcanic nature and the expected increase of anthropogenic activity related to future prospective mining activities and the establishment of the Transatlantic Trade and Investment Partnership (TTIP) between Europe and the USA. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Heavy metals and polychlorinated biphenyls (PCBs) sedimentation in the Lianhua Mountain Reservoir, Pearl River Delta, China.

    Science.gov (United States)

    Huang, Jingyu; Amuzu-Sefordzi, Basil; Li, Ming

    2015-05-01

    The Pearl River Delta is one of the biggest electronics manufacturing regions in the world. Due to the presence of abandoned industrial sites and the proliferation of large-scale electronics companies in the past four decades, it is therefore imperative to investigate the extent of heavy metals and polychlorinated biphenyls (PCBs) contamination in the region. Spatial and temporal distribution of heavy metals (Cr, Cu, Ni, Pb, and Zn) and PCBs (PCB28, PCB52, PCB101, PCB118, PCB138, PCB153, and PCB180) in the Lianhua Mountain reservoir in the Pearl River Delta, Dongguan City, China were examined based on a sedimentary profile analysis. Higher concentrations of the heavy metals detected were recorded in bottom sediments whereas 70% of the detected PCBs recorded maximum concentrations in top sediments. The geo-accumulation indices (Igeo) indicate that the study area is uncontaminated to moderately contaminated. Also, the integrated pollution indices (IPI) were above 1, except Pb, which shows that the study area is contaminated with heavy metals from anthropogenic sources. The concentrations of individual heavy metals and PCBs over a period of 60 years were also analyzed in order to establish a historical trend of pollution in the study area. This study provides baseline information on the level and historical trend of heavy metals and PCBs pollution in the study area.

  10. Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD.

    Science.gov (United States)

    Cherkasova, Mariya V; Faridi, Nazlie; Casey, Kevin F; O'Driscoll, Gillian A; Hechtman, Lily; Joober, Ridha; Baker, Glen B; Palmer, Jennifer; Dagher, Alain; Leyton, Marco; Benkelfat, Chawki

    2014-05-01

    Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.

  11. Studying placental transfer of highly purified non-dioxin-like PCBs in two models of the placental barrier

    DEFF Research Database (Denmark)

    Correia Carreira, S; Cartwright, L; Mathiesen, L

    2011-01-01

    Currently, toxicology and toxicokinetics of purified non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are poorly characterised. Transplacental kinetics of NDL-PCBs can be studied in a variety of models, but careful validation of each model is crucial. We aimed to develop a standard operating...

  12. PBDEs, PCBs, and DDE in eggs and their impacts on aplomado falcons (Falco femoralis) from Chihuahua and Veracruz, Mexico

    International Nuclear Information System (INIS)

    Mora, M.A.; Baxter, C.; Sericano, J.L.; Montoya, A.B.; Gallardo, J.C.; Rodriguez-Salazar, J.R.

    2011-01-01

    Eggs from aplomado falcons (Falco femoralis septentrionalis) nesting in Chihuahua and Veracruz, Mexico, were analyzed for organochlorine pesticides, PCBs, and PBDEs. p,p'-DDE was the only organochlorine found in all eggs at concentrations ranging from 0.13 to 7.85 μg/g wet weight. PCBs ranged from 0.04 to 2.80 μg/g wet weight and PBDEs from 62 to 798 ng/g lipid weight. DDE concentrations in eggs were not significantly different among regions; however, PCBs were significantly greater (P = 0.015) in Tinaja Verde, Chihuahua than in the other three regions. Also, PBDEs were significantly higher (P < 0.0001) in eggs from Veracruz than in those from Chihuahua. DDE concentrations in eggs were much lower than those associated with eggshell thinning. PBDEs and PCBs were lower than those reported in raptors from industrialized countries. Overall, contaminant concentrations observed suggest no likely impact on hatching success. The PBDE concentrations are among the first to be reported in raptor species in Mexico. - Highlights: → We analyzed environmental contaminants in eggs of aplomado falcons from Mexico. → Of all the organochlorine pesticides, only p,p'-DDE was detected in all the eggs. → Eggshell thickness was 20% thicker than the reported in eggshells from the 1970s. → Total PCBs and PBDEs were lower than those reported in industrialized countries. → Aplomado falcons in Mexico are currently not affected by DDE, PCBs, or PBDEs. - PBDEs, PCBs, and p,p'-DDE were not elevated in eggs and not likely to impact aplomado falcons in eastern and northern Mexico.

  13. PBDEs, PCBs, and DDE in eggs and their impacts on aplomado falcons (Falco femoralis) from Chihuahua and Veracruz, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Mora, M.A., E-mail: mmora@tamu.edu [Department of Wildlife and Fisheries Sciences, Texas A and M University, College Station, TX 77843-2258 (United States); Baxter, C. [Department of Wildlife and Fisheries Sciences, Texas A and M University, College Station, TX 77843-2258 (United States); Sericano, J.L. [Geochemical and Environmental Research Group, Texas A and M University, College Station, TX 77845 (United States); Montoya, A.B. [The Peregrine Fund, Inc, Boise, ID 83709 (United States); Gallardo, J.C. [Instituto de Neuroetologia, Universidad Veracruzana, Xalapa, Veracruz 91190 (Mexico); Rodriguez-Salazar, J.R. [The Peregrine Fund, Inc, Boise, ID 83709 (United States)

    2011-12-15

    Eggs from aplomado falcons (Falco femoralis septentrionalis) nesting in Chihuahua and Veracruz, Mexico, were analyzed for organochlorine pesticides, PCBs, and PBDEs. p,p'-DDE was the only organochlorine found in all eggs at concentrations ranging from 0.13 to 7.85 {mu}g/g wet weight. PCBs ranged from 0.04 to 2.80 {mu}g/g wet weight and PBDEs from 62 to 798 ng/g lipid weight. DDE concentrations in eggs were not significantly different among regions; however, PCBs were significantly greater (P = 0.015) in Tinaja Verde, Chihuahua than in the other three regions. Also, PBDEs were significantly higher (P < 0.0001) in eggs from Veracruz than in those from Chihuahua. DDE concentrations in eggs were much lower than those associated with eggshell thinning. PBDEs and PCBs were lower than those reported in raptors from industrialized countries. Overall, contaminant concentrations observed suggest no likely impact on hatching success. The PBDE concentrations are among the first to be reported in raptor species in Mexico. - Highlights: > We analyzed environmental contaminants in eggs of aplomado falcons from Mexico. > Of all the organochlorine pesticides, only p,p'-DDE was detected in all the eggs. > Eggshell thickness was 20% thicker than the reported in eggshells from the 1970s. > Total PCBs and PBDEs were lower than those reported in industrialized countries. > Aplomado falcons in Mexico are currently not affected by DDE, PCBs, or PBDEs. - PBDEs, PCBs, and p,p'-DDE were not elevated in eggs and not likely to impact aplomado falcons in eastern and northern Mexico.

  14. Identification of intracellular residues in the dopamine transporter critical for regulation of transporter conformation and cocaine binding

    DEFF Research Database (Denmark)

    Loland, Claus Juul; Grånäs, Charlotta; Javitch, Jonathan A

    2004-01-01

    Recently we showed evidence that mutation of Tyr-335 to Ala (Y335A) in the human dopamine transporter (hDAT) alters the conformational equilibrium of the transport cycle. Here, by substituting, one at a time, 16 different bulky or charged intracellular residues, we identify three residues, Lys-26...

  15. Dampened dopamine-mediated neuromodulation in prefrontal cortex of fragile X mice.

    Science.gov (United States)

    Paul, Kush; Venkitaramani, Deepa V; Cox, Charles L

    2013-02-15

    Fragile X syndrome (FXS) is the most common form of inheritable mental retardation caused by transcriptional silencing of the Fmr1 gene resulting in the absence of fragile X mental retardation protein (FMRP). The role of this protein in neurons is complex and its absence gives rise to diverse alterations in neuronal function leading to neurological disorders including mental retardation, hyperactivity, cognitive impairment, obsessive-compulsive behaviour, seizure activity and autism. FMRP regulates mRNA translation at dendritic spines where synapses are formed, and thus the lack of FMRP can lead to disruptions in synaptic transmission and plasticity. Many of these neurological deficits in FXS probably involve the prefrontal cortex, and in this study, we have focused on modulatory actions of dopamine in the medial prefrontal cortex. Our data indicate that dopamine produces a long-lasting enhancement of evoked inhibitory postsynaptic currents (IPSCs) mediated by D1-type receptors seen in wild-type mice; however, such enhancement is absent in the Fmr1 knock-out (Fmr1 KO) mice. The facilitation of IPSCs produced by direct cAMP stimulation was unaffected in Fmr1 KO, but D1 receptor levels were reduced in these animals. Our results show significant disruption of dopaminergic modulation of synaptic transmission in the Fmr1 KO mice and this alteration in inhibitory activity may provide insight into potential targets for the rescue of deficits associated with FXS.

  16. Dopamine D1 and D2 receptor immunoreactivities in the arcuate-median eminence complex and their link to the tubero-infundibular dopamine neurons

    Directory of Open Access Journals (Sweden)

    W. Romero-Fernandez

    2014-07-01

    Full Text Available Dopamine D1 and D2 receptor immunohistochemistry and Golgi techniques were used to study the structure of the adult rat arcuate-median eminence complex, and determine the distribution of the dopamine D1 and D2 receptor immunoreactivities therein, particularly in relation to the tubero-infundibular dopamine neurons. Punctate dopamine D1 and D2 receptor immunoreactivities, likely located on nerve terminals, were enriched in the lateral palisade zone built up of nerve terminals, while the densities were low to modest in the medial palisade zone. A codistribution of dopamine D1 receptor or dopamine D2 receptor immunoreactive puncta with tyrosine hydroxylase immunoreactive nerve terminals was demonstrated in the external layer. Dopamine D1 receptor but not dopamine D2 receptor immnunoreactivites nerve cell bodies were found in the ventromedial part of the arcuate nucleus and in the lateral part of the internal layer of the median eminence forming a continuous cell mass presumably representing neuropeptide Y immunoreactive nerve cell bodies. The major arcuate dopamine/ tyrosine hydroxylase nerve cell group was found in the dorsomedial part. A large number of tyrosine hydroxylase immunoreactive nerve cell bodies in this region demonstrated punctate dopamine D1 receptor immunoreactivity but only a few presented dopamine D2 receptor immunoreactivity which were mainly found in a substantial number of tyrosine hydroxylase cell bodies of the ventral periventricular hypothalamic nucleus, also belonging to the tubero-infundibular dopamine neurons. Structural evidence for projections of the arcuate nerve cells into the median eminence was also obtained. Distal axons formed horizontal axons in the internal layer issuing a variable number of collaterals classified into single or multiple strands located in the external layer increasing our understanding of the dopamine nerve terminal networks in this region.  Dopamine D1 and D2 receptors may therefore directly

  17. Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of SKF38393.

    NARCIS (Netherlands)

    Saigusa, T.; Aono, Y.; Sekino, R.; Uchida, T.; Takada, K.; Oi, Y.; Koshikawa, N.; Cools, A.R.

    2009-01-01

    Like dexamphetamine, SKF38393 induces an increase in striatal dopamine efflux which is insensitive for tetrodotoxin, Ca(2+) independent and prevented by a dopamine transporter inhibitor. The dexamphetamine-induced striatal dopamine efflux originates from both the reserpine-sensitive vesicular

  18. Polychlorinated biphenyls (PCBs) in industrial and municipal effluents: Concentrations, congener profiles, and partitioning onto particulates and organic carbon

    Energy Technology Data Exchange (ETDEWEB)

    Balasubramani, Aparna, E-mail: aparna.27889@gmail.com; Howell, Nathan L., E-mail: nlhowell@central.uh.edu; Rifai, Hanadi S., E-mail: rifai@uh.edu

    2014-03-01

    Wastewater effluent samples were collected in the summer of 2009 from 16 different locations which included municipal and industrial wastewater treatment plants and petrochemical industrial outfalls in the Houston area. The effluent samples were analyzed for all 209 polychlorinated biphenyls (PCBs) congeners using high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) using the USEPA method 1668A. The total PCBs (∑ 209) concentration in the dissolved medium ranged from 1.01 to 8.12 ng/L and ranged from 2.03 to 31.2 ng/L in the suspended medium. Lighter PCB congeners exhibited highest concentrations in the dissolved phase whereas, in the suspended phase, heavier PCBs exhibited the highest concentrations. The PCB homolog concentrations were dominated by monochlorobiphenyls through hexachlorobiphenyls, with dichlorobiphenyls exhibiting the highest concentration amongst them at most of the effluent outfalls, in the suspended phase. Both total suspended solids (TSS) and various organic carbon fractions played an important role in the distribution of the suspended fractions of PCBs in the effluents. The log K{sub oc} values determined in the effluents suggest that effluent PCB loads might have more risk and impact than what standard partitioning models predict. - Highlights: • 209 PCB congeners were measured in 16 different municipal and industrial effluents. • PCB congener differences were elucidated for the various effluent types. • In addition to log K{sub ow}, organic carbon and TSS affect partitioning of PCBs. • High concentrations of homolog 2 maybe due to biotransformation of PCBs.

  19. Polychlorinated biphenyls (PCBs) in industrial and municipal effluents: Concentrations, congener profiles, and partitioning onto particulates and organic carbon

    International Nuclear Information System (INIS)

    Balasubramani, Aparna; Howell, Nathan L.; Rifai, Hanadi S.

    2014-01-01

    Wastewater effluent samples were collected in the summer of 2009 from 16 different locations which included municipal and industrial wastewater treatment plants and petrochemical industrial outfalls in the Houston area. The effluent samples were analyzed for all 209 polychlorinated biphenyls (PCBs) congeners using high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) using the USEPA method 1668A. The total PCBs (∑ 209) concentration in the dissolved medium ranged from 1.01 to 8.12 ng/L and ranged from 2.03 to 31.2 ng/L in the suspended medium. Lighter PCB congeners exhibited highest concentrations in the dissolved phase whereas, in the suspended phase, heavier PCBs exhibited the highest concentrations. The PCB homolog concentrations were dominated by monochlorobiphenyls through hexachlorobiphenyls, with dichlorobiphenyls exhibiting the highest concentration amongst them at most of the effluent outfalls, in the suspended phase. Both total suspended solids (TSS) and various organic carbon fractions played an important role in the distribution of the suspended fractions of PCBs in the effluents. The log K oc values determined in the effluents suggest that effluent PCB loads might have more risk and impact than what standard partitioning models predict. - Highlights: • 209 PCB congeners were measured in 16 different municipal and industrial effluents. • PCB congener differences were elucidated for the various effluent types. • In addition to log K ow , organic carbon and TSS affect partitioning of PCBs. • High concentrations of homolog 2 maybe due to biotransformation of PCBs

  20. Reproduction of European eel jeopardised by high levels of dioxins and dioxin-like PCBs?

    Science.gov (United States)

    Geeraerts, C; Focant, J-F; Eppe, G; De Pauw, E; Belpaire, C

    2011-09-01

    Dioxins, furans and dioxin-like polychlorinated biphenyls (PCBs) were analysed in muscle tissue from yellow phased European eel (Anguilla anguilla) from 38 sites in Belgium. Dioxin concentrations in eel vary considerably between sampling locations, indicating that yellow eel is a good indicator of local pollution levels. Measured levels of dioxin-like PCBs are much higher than those of the dioxins and furans. In the majority of the sites, eel has levels considered to be detrimental for their reproduction. Field levels of dioxin and dioxin-like PCBs are therefore suggested as an additional causal factor contributing to the decline of the European eel. 42% of the sampling sites show especially dioxin-like PCB levels exceeding the European consumption level (with a factor 3 on average). Human consumption of eel, especially in these highly contaminated sites, seems unjustified. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation.

    Science.gov (United States)

    Beeler, Jeff A; Faust, Rudolf P; Turkson, Susie; Ye, Honggang; Zhuang, Xiaoxi

    2016-06-01

    The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a reward deficiency and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. The KD mice did not gain more weight or show increased appetitive motivation compared with wild-type mice in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than wild-type mice, obtaining no protective benefit from exercise opportunities. These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Effects of standard humic materials on relative bioavailability of NDL-PCBs in juvenile swine.

    Directory of Open Access Journals (Sweden)

    Matthieu Delannoy

    Full Text Available Young children with their hand-to-mouth activity may be exposed to contaminated soils. However few studies assessing exposure of organic compounds sequestrated in soil were realized. The present study explores the impact of different organic matters on retention of NDL-PCBs during digestive processes using commercial humic substances in a close digestive model of children: the piglet. Six artificial soils were used. One standard soil, devoid of organic matter, and five amended versions of this standard soil with either fulvic acid, humic acid, Sphagnum peat, activated carbon or a mix of Sphagnum peat and activated carbon (95∶5 (SPAC were prepared. In order to compare the different treatments, we use spiked oil and negative control animals. Forty male piglets were randomly distributed in 7 contaminated and one control groups (n = 5 for each group. During 10 days, the piglets were fed artificial soil or a corn oil spiked with 19,200 ng of Aroclor 1254 per g of dry matter (6,000 ng.g⁻¹ of NDL-PCBs to achieve an exposure dose of 1,200 ng NDL-PCBs.Kg⁻¹ of body weight per day. NDL-PCBs in adipose tissue were analyzed by GC-MS. Fulvic acid reduced slightly the bioavailability of NDL-PCBs compared to oil. Humic acid and Sphagnum peat reduced it significantly higher whereas activated carbon reduced the most. Piglets exposed to soil containing both activated carbon and Shagnum peat exhibited a lower reduction than soil with only activated carbon. Therefore, treatment groups are ordered by decreasing value of relative bioavailability as following: oil ≥ fulvic acid>Sphagnum peat ≥ Sphagnum peat and activated carbon ≥ Humic acid>>activated carbon. This suggests competition between Sphagnum peat and activated carbon. The present study highlights that quality of organic matter does have a significant effect on bioavailability of sequestrated organic compounds.

  3. Stereoselectivity of presynaptic autoreceptors modulating dopamine release

    International Nuclear Information System (INIS)

    Arbilla, S.; Langer, S.Z.

    1981-01-01

    The effects of the (R)- and (S)-enantiomers of sulpiride and butaclamol were studied on the spontaneous and field stimulation-evoked release of total radioactivity from slices of rabbit caudate nucleus prelabelled with [ 3 H]dopamine. (S)-Sulpiride in concentrations ranging from 0.01-1μM enhanced the electrically evoked release of [ 3 H]dopamine while (R)-sulpiride was 10 times less potent than (S)-sulpiride. Exposure to (S)-butaclamol (0.1-1 μM) but not to (R)-butaclamol (0.1-10μM) enhanced the field-stimulated release of [ 3 H]dopamine. The facilitatory effects of (S)- and (R)-sulpiride and (S)-butaclamol on the stimulated release of the labelled neurotransmitter were observed under conditions in which these drugs did not modify the spontaneous outflow of radioactivity. Only the active enantiomers of sulpiride and butaclamol antagonized the inhibition by apomorphine (1μM) of the stimulated release of [ 3 H]dopamine. Our results indicate that the presynaptic inhibitory dopamine autoreceptors modulating the stimulation-evoked release of [ 3 H]dopamine in the caudate nucleus are, like the classical postsynaptic dopamine receptors, chemically stereoselective. (Auth.)

  4. Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation.

    Directory of Open Access Journals (Sweden)

    Matthew T C Brown

    2010-12-01

    Full Text Available Addictive drugs have in common that they cause surges in dopamine (DA concentration in the mesolimbic reward system and elicit synaptic plasticity in DA neurons of the ventral tegmental area (VTA. Cocaine for example drives insertion of GluA2-lacking AMPA receptors (AMPARs at glutamatergic synapes in DA neurons. However it remains elusive which molecular target of cocaine drives such AMPAR redistribution and whether other addictive drugs (morphine and nicotine cause similar changes through their effects on the mesolimbic DA system.We used in vitro electrophysiological techniques in wild-type and transgenic mice to observe the modulation of excitatory inputs onto DA neurons by addictive drugs. To observe AMPAR redistribution, post-embedding immunohistochemistry for GluA2 AMPAR subunit was combined with electron microscopy. We also used a double-floxed AAV virus expressing channelrhodopsin together with a DAT Cre mouse line to selectively express ChR2 in VTA DA neurons. We find that in mice where the effect of cocaine on the dopamine transporter (DAT is specifically blocked, AMPAR redistribution was absent following administration of the drug. Furthermore, addictive drugs known to increase dopamine levels cause a similar AMPAR redistribution. Finally, activating DA VTA neurons optogenetically is sufficient to drive insertion of GluA2-lacking AMPARs, mimicking the changes observed after a single injection of morphine, nicotine or cocaine.We propose the mesolimbic dopamine system as a point of convergence at which addictive drugs can alter neural circuits. We also show that direct activation of DA neurons is sufficient to drive AMPAR redistribution, which may be a mechanism associated with early steps of non-substance related addictions.

  5. GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra.

    Science.gov (United States)

    Engberg, G; Kling-Petersen, T; Nissbrandt, H

    1993-11-01

    Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularization of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularization of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons.

  6. 6-hydroxydopamine-induced degeneration of nigral dopamine neurons: differential effect on nigral and striatal D-1 dopamine receptors

    International Nuclear Information System (INIS)

    Porceddu, M.L.; Giorgi, O.; De Montis, G.; Mele, S.; Cocco, L.; Ongini, E.; Biggio, G.

    1987-01-01

    Dopamine-sensitive adenylate cyclase and 3 H-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of 3 H-SCH 23390 to rat nigral D-1 dopamine receptors were markedly decreased after the lesion. On the contrary, 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway enhanced both adenylate cyclase activity and the density of 3 H-SCH 23390 binding sites in striatal membrane preparations. The changes in 3 H-SCH 23390 binding found in both nigral and striatal membrane preparations were associated with changes in the total number of binding sites with no modifications in their apparent affinity. The results indicate that: a) within the substantia nigra a fraction (30%) of D-1 dopamine receptors coupled to the adenylate cyclase is located on cell bodies and and/or dendrites of dopaminergic neurons; b) striatal D-1 dopamine receptors are tonically innervated by nigrostriatal afferent fibers. 24 references, 1 figure, 1 table

  7. Dopamine reward prediction error coding.

    Science.gov (United States)

    Schultz, Wolfram

    2016-03-01

    Reward prediction errors consist of the differences between received and predicted rewards. They are crucial for basic forms of learning about rewards and make us strive for more rewards-an evolutionary beneficial trait. Most dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error; they are activated by more reward than predicted (positive prediction error), remain at baseline activity for fully predicted rewards, and show depressed activity with less reward than predicted (negative prediction error). The dopamine signal increases nonlinearly with reward value and codes formal economic utility. Drugs of addiction generate, hijack, and amplify the dopamine reward signal and induce exaggerated, uncontrolled dopamine effects on neuronal plasticity. The striatum, amygdala, and frontal cortex also show reward prediction error coding, but only in subpopulations of neurons. Thus, the important concept of reward prediction errors is implemented in neuronal hardware.

  8. Dopamine D2 receptors mediate two-odor discrimination and reversal learning in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Grandy David K

    2004-04-01

    Full Text Available Abstract Background Dopamine modulation of neuronal signaling in the frontal cortex, midbrain, and striatum is essential for processing and integrating diverse external sensory stimuli and attaching salience to environmental cues that signal causal relationships, thereby guiding goal-directed, adaptable behaviors. At the cellular level, dopamine signaling is mediated through D1-like or D2-like receptors. Although a role for D1-like receptors in a variety of goal-directed behaviors has been identified, an explicit involvement of D2 receptors has not been clearly established. To determine whether dopamine D2 receptor-mediated signaling contributes to associative and reversal learning, we compared C57Bl/6J mice that completely lack functional dopamine D2 receptors to wild-type mice with respect to their ability to attach appropriate salience to external stimuli (stimulus discrimination and disengage from inappropriate behavioral strategies when reinforcement contingencies change (e.g. reversal learning. Results Mildly food-deprived female wild-type and dopamine D2 receptor deficient mice rapidly learned to retrieve and consume visible food reinforcers from a small plastic dish. Furthermore, both genotypes readily learned to dig through the same dish filled with sterile sand in order to locate a buried food pellet. However, the dopamine D2 receptor deficient mice required significantly more trials than wild-type mice to discriminate between two dishes, each filled with a different scented sand, and to associate one of the two odors with the presence of a reinforcer (food. In addition, the dopamine D2 receptor deficient mice repeatedly fail to alter their response patterns during reversal trials where the reinforcement rules were inverted. Conclusions Inbred C57Bl/6J mice that develop in the complete absence of functional dopamine D2 receptors are capable of olfaction but display an impaired ability to acquire odor-driven reinforcement contingencies

  9. Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure

    Directory of Open Access Journals (Sweden)

    Jamie H. Rose

    2016-07-01

    Full Text Available The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc κ opioid receptors (KOR in chronic intermittent ethanol (CIE exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs.

  10. Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure

    Science.gov (United States)

    Rose, Jamie H.; Karkhanis, Anushree N.; Steiniger-Brach, Björn; Jones, Sara R.

    2016-01-01

    The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc) κ opioid receptors (KOR) in chronic intermittent ethanol (CIE) exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs. PMID:27472317

  11. Membrane permeable C-terminal dopamine transporter peptides attenuate amphetamine-evoked dopamine release

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Owens, WA; Winkler, Marie-Therese

    2013-01-01

    The dopamine transporter (DAT) is responsible for sequestration of extracellular dopamine (DA). The psychostimulant amphetamine (AMPH) is a DAT substrate, which is actively transported into the nerve terminal, eliciting vesicular depletion and reversal of DA transport via DAT. Here, we investigate......-terminal protein-protein interactions are critical for AMPH-evoked DA efflux and suggest that it may be possible to target protein-protein interactions to modulate transporter function and interfere with psychostimulant effects....

  12. Non-Dioxin-Like PCBs: Effects and Consideration In Ecological Risk Assessment

    Science.gov (United States)

    An estimated one million metric tons of commercial mixtures of polychlorinated biphenyls (PCBs), such as Aroclors (USA), Kanechlors (Japan) and Clophens (Germany), were manufactured (WHO, 1993) and used worldwide as dielectric fluids

  13. Air-sea gas exchange of HCHs and PCBs and enantiomers of α-HCH in the Kattegat Sea region

    International Nuclear Information System (INIS)

    Sundqvist, Kristina L.; Wingfors, Haakan; Brorstoem-Lunden, Eva; Wiberg, Karin

    2004-01-01

    Concentrations and air-water gas exchange of polychlorinated biphenyls (PCBs) and hexachlorocyclohexanes (HCHs) were determined in nine paired air and water samples. The samples were collected monthly in the Kattegat Sea between December 1998 and November 1999. Average fugacity and flux values indicated that PCBs were oversaturated in the water, while HCHs were net deposited. Variations were large over the year, especially during spring and summer. Air parcel back trajectories suggested that air concentrations over the Kattegat Sea are largely dependent of air mass origin. Seasonal trends were detected for airborne HCHs and for PCBs in water. The air and water enantiomeric compositions of α-HCH indicated that a larger portion of α-HCH in air originated from the underlying water during summer than during winter. - Air-water exchange of PCBs and HCHs is studied in the Kattegat Sea and shows to vary seasonally

  14. Contamination by polychlorinated biphenyls (PCBs) in striped dolphins (Stenella coeruleoalba) from the Southeastern Mediterranean Sea.

    Science.gov (United States)

    Storelli, Maria Maddalena; Barone, Grazia; Giacominelli-Stuffler, Roberto; Marcotrigiano, Giuseppe Onofrio

    2012-09-01

    Concentrations of polychlorinated biphenyls (PCBs) including dioxin-like PCBs (non-ortho, PCB 77, PCB 126, and PCB 169 and mono-ortho, PCB 105, PCB 118, and PCB 156) were measured in different organs and tissues (melon, blubber, liver, kidney, lung, heart, and muscle tissue) of striped dolphins (Stenella coeruleoalba) from the Eastern Mediterranean Sea (Adriatic Sea). The mean highest levels were in blubber and melon, followed by liver, kidney, lung, heart, and muscle tissue. PCB profiles were similar in all tissues and organs being dominated by the higher chlorinated homologues (hexa-CBs, 55.8-62.1%; penta-CBs, 15.4-20.0%; and hepta-CB PCB 180, 12.7-16.5%). Major PCBs in all tissues were congeners 138 and 153 collectively accounting for 50.6-58.3% of the total PCB concentrations, followed by PCB 101, 105, 118, and 180 constituting from 27.0% to 31.0%. PCB levels were higher in adult males than in adult females. The estimated 2,3,7,8-TCDD toxic equivalents of non- and mono-ortho PCBs were much higher than the threshold level above which adverse effects have been observed in other marine mammals species, suggesting that striped dolphins in this region are at risk for toxic effects.

  15. Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and biphenyls (PCBs) in home-produced eggs.

    Science.gov (United States)

    Hoogenboom, Ron L A P; Ten Dam, Guillaume; van Bruggen, Mark; Jeurissen, Suzanne M F; van Leeuwen, Stefan P J; Theelen, Rob M C; Zeilmaker, Marco J

    2016-05-01

    Home produced eggs from 62 addresses in the Netherlands were investigated for the levels of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and biphenyls (PCBs), both dioxin-like (dl) and non-dioxin-like (ndl). Compared to commercial eggs, levels were relatively high with a median of 4.6 pg TEQ g(-1) fat for the sum of PCDD/Fs and dl-PCBs, and a highest level of 18.9 pg TEQ g(-1) fat. A number of samples showed clearly elevated ndl-PCB levels with a median of 13 ng g(-1) fat and a highest level of 80 ng g(-1) fat. There were no clear regional differences, even though part of the samples were derived from the rather industrial Rotterdam/Rijnmond area. Based on the congener patterns, former backyard burning of waste seems the most likely source for most eggs, with two exceptions where other sources contributed to the contamination. Similar is true for the ndl-PCBs. The study shows that average levels are about ten-fold higher than commercial eggs and may substantially contribute to the intake of PCDD/Fs and dl-PCBs by consumers. Intervention measures to reduce the intake of these contaminants by laying hens are advised. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Science.gov (United States)

    Parnaudeau, Sébastien; Dongelmans, Marie-louise; Turiault, Marc; Ambroggi, Frédéric; Delbes, Anne-Sophie; Cansell, Céline; Luquet, Serge; Piazza, Pier-Vincenzo; Tronche, François; Barik, Jacques

    2014-01-01

    The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs) release. GCs bind the glucocorticoid receptor (GR) a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While GR within dopamine-innervated areas drives cocaine's behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurons is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice. PMID:24574986

  17. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Directory of Open Access Journals (Sweden)

    Sebastien eParnaudeau

    2014-02-01

    Full Text Available The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs release. GCs bind the glucocorticoid receptor (GR a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While the GR within dopamine-innervated areas drives cocaine’s behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurones is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice.

  18. Dietary exposure to non-dioxin-like PCBs of different population groups in Austria.

    Science.gov (United States)

    Mihats, Daniela; Moche, Wolfgang; Prean, Michael; Rauscher-Gabernig, Elke

    2015-05-01

    The dietary exposure to the sum of the six indicator PCBs (Σ6 PCBs; PCB 28, 52, 101, 138, 153, and 180) across different Austrian population groups was assessed in this study by combining data on occurrence from food of the Austrian market (n=157) analysed during 2006-2011 with national food consumption data. The most contaminated food group was meat, poultry, game and offal with average levels of ndl-PCBs of 5.20 ng g(-1) fat. In fish and fish products and eggs, mean concentrations of 3.89 ng g(-1) fresh weight (fw) and 4.00 ng g(-1) fat, respectively, were found. In milk and dairy products average concentrations ranged from 3.07 to 4.44 ng g(-1) fat. The mean dietary intake of Σ6 PCBs was estimated to be 3.37 ng kg(-1) bw d(-1) for children (6-15 years old), 3.19 ng kg(-1) bw d(-1) for women (19-65 years) and 2.64 ng kg(-1) bw d(-1) for men (19-65 years). In all three population groups, milk and dairy products was the major contributing food group to the total dietary intake (50-55%) followed by fish and fish products (23-27%). The exposure of all Austrian population groups is well below the tolerable daily intake (TDI) of 10 ng kg(-1) bw d(-1) proposed by WHO, accounting for 34% in children, 32% in women and 26% in men. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Cerebral vascular effects of hypovolemia and dopamine infusions

    DEFF Research Database (Denmark)

    Holst Hahn, Gitte; Heiring, Christian; Pryds, Ole

    2012-01-01

    Despite widespread use, effects of volume boluses and dopamine in hypotensive newborn infants remain controversial. We aimed to elucidate if hypovolemia alone impairs cerebral autoregulation (CA) and if dopamine affects cerebral vasculature.......Despite widespread use, effects of volume boluses and dopamine in hypotensive newborn infants remain controversial. We aimed to elucidate if hypovolemia alone impairs cerebral autoregulation (CA) and if dopamine affects cerebral vasculature....

  20. Serotonin-S2 and dopamine-D2 receptors are the same size in membranes

    International Nuclear Information System (INIS)

    Brann, M.R.

    1985-01-01

    Target size analysis was used to compare the sizes of serotonin-S2 and dopamine-D2 receptors in rat brain membranes. The sizes of these receptors were standardized by comparison with the muscarinic receptor, a receptor of known size. The number of serotonin-S2 receptors labeled with (3H)ketanserin or (3H)spiperone in frontal cortex decreased as an exponential function of radiation dose, and receptor affinity was not affected. The number of dopamine-D2 receptors labeled with (3H)spiperone in striatum also decreased as an exponential function of radiation dose, and D2 and S2 receptors were equally sensitive to radiation. In both striatum and frontal cortex, the number of muscarinic receptors labeled with (3H)QNB decreased as an exponential function of radiation dose, and were much less sensitive to radiation than S2 and D2 receptors. These data indicate that in rat brain membranes, S2 and D2 receptors are of similar size, and both molecules are much larger than the muscarinic receptor

  1. Comparison of supercritical fluid extraction and Soxhlet extraction for the determination of PCBs in seaweed samples.

    Science.gov (United States)

    Punín Crespo, M O; Lage Yusty, M A

    2005-06-01

    The efficiency of supercritical fluid extraction for the determination of 12 polychlorinated biphenyls from algae samples is compared to Soxhlet extraction. Analytical detection limits for the individual congeners ranged from 0.62 microgl(-1) to 19 microgl(-1). Recovery was tested for both methods using standard addition procedure. At maximum spike level of concentration, the mean recoveries were not significantly different (P>0.05) of all PCBs studied, with the exception of PCBs 28, 52, 77 and 169. Method precision for Soxhlet extraction (yield comparable results, SFE offers the advantage of detecting all PCBs studied at lower concentrations, reducing extraction time, and reducing the amount of solvents needed. The optimized methods were applied to the analysis of three real seaweed samples, except for PCB101 the concentrations of all PCBs were low or below the detection limits. The levels of PCB101 found in sample 1 were 6.6+/-0.54 ng g(-1) d.w., in sample 2 the levels were 8.2+/-0.86 ng g(-1) d.w. and in sample 3 they were 7.7+/-0.08 ng g(-1) d.w.

  2. Optimization of pressurized liquid extraction (PLE) of dioxin-furans and dioxin-like PCBs from environmental samples.

    Science.gov (United States)

    Antunes, Pedro; Viana, Paula; Vinhas, Tereza; Capelo, J L; Rivera, J; Gaspar, Elvira M S M

    2008-05-30

    Pressurized liquid extraction (PLE) applying three extraction cycles, temperature and pressure, improved the efficiency of solvent extraction when compared with the classical Soxhlet extraction. Polychlorinated-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like PCBs (coplanar polychlorinated biphenyls (Co-PCBs)) in two Certified Reference Materials [DX-1 (sediment) and BCR 529 (soil)] and in two contaminated environmental samples (sediment and soil) were extracted by ASE and Soxhlet methods. Unlike data previously reported by other authors, results demonstrated that ASE using n-hexane as solvent and three extraction cycles, 12.4 MPa (1800 psi) and 150 degrees C achieves similar recovery results than the classical Soxhlet extraction for PCDFs and Co-PCBs, and better recovery results for PCDDs. ASE extraction, performed in less time and with less solvent proved to be, under optimized conditions, an excellent extraction technique for the simultaneous analysis of PCDD/PCDFs and Co-PCBs from environmental samples. Such fast analytical methodology, having the best cost-efficiency ratio, will improve the control and will provide more information about the occurrence of dioxins and the levels of toxicity and thereby will contribute to increase human health.

  3. Simultaneous determination of aliphatic hydrocarbons, PCBs and PCTs in pork liver by gas chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Barros, C [Dept. de Quimica Analitica, Nutricion y Bromatologia, Area Nutricion y Bromatologia, Facultad de Farmacia, Santiago de Compostela (Spain); Alvarez Pineiro, M E [Inst. de Investigacion y Analisis Alimentarios, Lab. de Bromatologia, Facultad de Farmacia, Santiago de Compostela (Spain); Simal Lozano, J [Dept. de Quimica Analitica, Nutricion y Bromatologia, Area Nutricion y Bromatologia, Facultad de Farmacia, Santiago de Compostela (Spain); Lage Yusty, M A [Inst. de Investigacion y Analisis Alimentarios, Lab. de Bromatologia, Facultad de Farmacia, Santiago de Compostela (Spain)

    1996-10-01

    A multicomponent extraction/concentration procedure has been developed for the enrichment of PCBs, PCTs and aliphatic hydrocarbons (pristane, C{sub 18}, C{sub 19}, C{sub 20}, C{sub 22}, C{sub 24}, C{sub 28}, C{sub 32} and C{sub 36}) in pork liver. These components of the enriched extract were then simultaneously determined by gas chromatography. Mean recoveries ranged from 81.5% for pristane to 93% for PCBs; CV % (0.9-6.7) indicated the method to be both precise and reproducible. (orig.)

  4. Photodegradation of Selected PCBs in the Presence of Nano-TiO2 as Catalyst and H2O2 as an Oxidant

    Directory of Open Access Journals (Sweden)

    Hongtao Yu

    2010-11-01

    Full Text Available Photodegradation of five strategically selected PCBs was carried out in acetonitrile/water 80:20. Quantum chemical calculations reveal that PCBs without any chlorine on ortho-positions are closer to be planar, while PCBs with at least one chlorine atoms at the ortho-positions causes the two benzene rings to be nearly perpendicular. Light-induced degradation of planar PCBs is much slower than the perpendicular ones. The use of nano-TiO2 speeds up the degradation of the planar PCBs, but slows down the degradation of the non-planar ones. The use of H2O2 speeds up the degradation of planar PCBs greatly (by >20 times, but has little effect on non-planar ones except 2,3,5,6-TCB. The relative photodegradation rate is: 2,2’,4,4’-TCB > 2,3,5,6-TCB > 2,6-DCB ≈ 3,3’,4,4’-TCB > 3,4’,5-TCB. The use of H2O2 in combination with sunlight irradiation could be an efficient and “green” technology for PCB remediation.

  5. Fate of PCBs, PAHs and their source characteristic ratios during composting and digestion of source-separated organic waste in full-scale plants

    International Nuclear Information System (INIS)

    Braendli, Rahel C.; Bucheli, Thomas D.; Kupper, Thomas; Mayer, Jochen; Stadelmann, Franz X.; Tarradellas, Joseph

    2007-01-01

    Composting and digestion are important waste management strategies. However, the resulting products can contain significant amounts of organic pollutants such as polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). In this study we followed the concentration changes of PCBs and PAHs during composting and digestion on field-scale for the first time. Concentrations of low-chlorinated PCBs increased during composting (about 30%), whereas a slight decrease was observed for the higher chlorinated congeners (about 10%). Enantiomeric fractions of atropisomeric PCBs were essentially racemic and stable over time. Levels of low-molecular-weight PAHs declined during composting (50-90% reduction), whereas high-molecular-weight compounds were stable. The PCBs and PAHs concentrations did not seem to vary during digestion. Source apportionment by applying characteristic PAH ratios and molecular markers in input material did not give any clear results. Some of these parameters changed considerably during composting. Hence, their diagnostic potential for finished compost must be questioned. - During field-scale composting, low molecular weight PCBs and PAHs increased and decreased, respectively, whereas high molecular weight compounds remained stable

  6. Depuration of PCBS and DDTS in mullet under captivity conditions

    Energy Technology Data Exchange (ETDEWEB)

    Antunes, P.; Gil, O.; Vale, C. [Inst. Nacional de Investigacao Agraria e das Pescas/IPIMAR, Lisboa (Portugal); Ferreira, M. [ICBAS-Inst. de Ciencias Biomedicas Abel Salazar, Porto (Portugal); Reis-Henriques, M.A. [CIIMAR-Centro Interdisciplinar de Investigacao Marinha e Ambiental, Porto (Portugal)

    2004-09-15

    Fish captured in the coastal zone and estuaries often contains enhanced residues of organochlorine compounds in their tissues, in response to environmental contamination. Residues in fish tissues may be eliminated by different pathways, but most of what is known comes from laboratory studies with species that are exposed to contaminants. In recent years, the importance of ethoxyresorufin O-deethylase (EROD), one of the hepatic cytochrome P-450 dependent monooxidase, has become widely known, and it is increasingly accepted as an indicator of exposure to common organic pollutants. The mullet (Mugil cephalus) from the Douro estuary may present relatively high content of PCBs and DDTs. The objective of this study was to examine the levels of PCBs and DDTs in muscle and liver when individuals are exposed to clean sea water and uncontaminated food, and to evaluate whether this is a feasible option for depuration.

  7. Spatial variation of PAHs and PCBs in coastal air, seawater, and sediments in a heavily industrialized region.

    Science.gov (United States)

    Odabasi, Mustafa; Dumanoglu, Yetkin; Kara, Melik; Altiok, Hasan; Elbir, Tolga; Bayram, Abdurrahman

    2017-05-01

    Concurrent coastal seawater (n = 22), sediment (n = 22), and atmospheric samples (n = 10) were collected in the Aliaga industrial region, Turkey, to explore the spatial variation, sources, and air-seawater exchange of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Seawater Σ 16 PAH concentrations (particle + dissolved) ranged between 5107 and 294,624 pg L -1 , while Σ 41 PCB concentrations were in the range of 880-50,829 pg L -1 . Levels in sediments were highly variable ranging between 35.5-49,682 and 2.7-2450 μg kg -1 in dry weight for Σ 16 PAHs and Σ 41 PCBs, respectively. Atmospheric concentrations varied between 1791-274,974 and 104-20,083 pg m -3 for Σ 16 PAHs and Σ 41 PCBs, respectively. Sediment organic matter (OM) content and levels of Σ 16 PAHs and Σ 41 PCBs correlated weakly (r 2  = 0.19-0.23, p seawater, and sediment and factor analysis on the sediment levels pointed out that the major sources in the region are steel plants, petroleum refinery, petrochemical complex, ship breaking, loading/unloading activities at the ports, vehicular emissions, and fossil fuel combustion emissions. The direction of the air-seawater exchange was also explored by estimating seawater fugacity fractions of PAHs and PCBs. For PAHs, the number of cases implying deposition (43.0%) and volatilization (39.5%) was similar, while for PCBs, the number of cases implying volatilization (60.4%) was much higher compared to deposition (21.6%). Fugacity fractions were generally seawater and sediment levels were measured, implying that atmospheric deposition is an important mechanism affecting seawater and sediment PAH and PCB levels.

  8. PCDDs, PCDFs, and coplanar PCBs in albatross from the North Pacific and Southern Oceans: levels, patterns, and toxicological implications.

    Science.gov (United States)

    Tanabe, Shinsuke; Watanabe, Mafumi; Minh, Tu Binh; Kunisue, Tatsuya; Nakanishi, Shigeyuki; Ono, Hitoshi; Tanaka, Hiroyuki

    2004-01-15

    Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (coplanar PCBs) were determined in five albatross species collected from the North Pacific and Southern Oceans to assess the north-south differences in residue levels, accumulation patterns, and toxic potential. Black-footed and Laysan albatrosses from the North Pacific Ocean contained higher levels of PCDD/Fs and coplanar PCBs than albatrosses from the Southern Ocean, indicating that emission sources of these contaminants were predominant in the northern hemisphere. Residue levels in albatrosses from the remote North Pacific Ocean far from the point source of pollution were comparable to or higher than those in terrestrial and coastal birds from contaminated areas in developed nations, suggesting the specific exposure and accumulation of PCDD/Fs and coplanar PCBs in albatross. The long life span and ingestion of plastic resin pellets by albatrosses could be the plausible explanations for the elevated accumulation of persistent and lipophilic contaminants including PCDD/Fs and coplanar PCBs in these birds. Relative proportions of PCDFs and coplanar PCBs in albatross were higher than those observed in birds inhabiting terrestrial and coastal areas, suggesting that these toxic chemicals may have higher transportability by air and water than PCDDs. Congener patterns of PCDD/Fs in albatross showed less variability as compared to those in terrestrial species, indicating that contamination patterns of PCDD/Fs were similar within the open ocean environment. Contributions of PCDD/Fs to total TEQs in albatrosses from the open ocean were generally lower than those in terrestrial birds, suggesting different toxic potency of PCDD/Fs and coplanar PCBs on animals inhabiting open ocean and terrestrial environment. Whereas albatrosses from southern oceans retained lower TEQ concentrations, possible adverse effects of PCDD/Fs and coplanar PCBs

  9. A question of origin: dioxin-like PCBs and their relevance in stock management of European eels.

    Science.gov (United States)

    Freese, Marko; Sühring, Roxana; Pohlmann, Jan-Dag; Wolschke, Hendrik; Magath, Victoria; Ebinghaus, Ralf; Hanel, Reinhold

    2016-01-01

    The stock of European Eel (Anguilla anguilla L.) has reached an all-time low in 2011. Spawner quality of mature eels in terms of health status and fitness is considered one of the key elements for successful migration and reproduction. Dioxin-like Polychlorinated Biphenyls (dl-PCBs) are known persistent organic pollutants potentially affecting the reproductive capability and health status of eels throughout their entire lifetime. In this study, muscle tissue samples of 192 European eels of all continental life stages from 6 different water bodies and 13 sampling sites were analyzed for contamination with lipophilic dl-PCBs to investigate the potential relevance of the respective habitat in light of eel stock management. Results of this study reveal habitat-dependent and life history stage-related accumulation of targeted PCBs. Sum concentrations of targeted PCBs differed significantly between life stages and inter-habitat variability in dl-PCB levels and -profiles was observed. Among all investigated life stages, migrant silver eels were found to be the most suitable life history stage to represent their particular water system due to habitat dwell-time and their terminal contamination status. With reference to a possible negative impact of dl-PCBs on health and the reproductive capability of eels, it was hypothesized that those growing up in less polluted habitats have a better chance to produce healthy offspring than those growing up in highly polluted habitats. We suggest that the contamination status of water systems is fundamental for the life cycle of eels and needs to be considered in stock management and restocking programs.

  10. PCBs with immersion tin finish - some experiences with lead-free reflow process

    Energy Technology Data Exchange (ETDEWEB)

    Bukat, K.; Koziol, G.; Sitek, J.; Borecki, J.; Hackiewicz, H. [Tele and Radio Research Inst., Warsaw (Poland); Merkle, H.; Schroeder, S. [Ormecon Chemie GmbH and Co. KG, Ammersbek (Germany); Girulska, A.; Gardela, K. [Eldos Sp. z o.o., Wroclaw (Poland)

    2004-07-01

    Substitution of lead-free solders in electronic assemblies requires changes in the conventional SnPb finishes of PCBs. The Craft project ''PRINT'' objectives respond to this challenge. Its main goal is to develop and implement the new technology of high solderability immersion tin for printed circuit boards at small and medium enterprises. The subject of the research was organic based immersion tin coating which would fulfil demands of SMT. In the paper the results of reflow soldering process on PCBs covered by Ormecon registered immersion tin finish with using lead-free solder pastes will be described. Solderability of tin coating as well as wettability of lead-free solder paste will be presented. (orig.)

  11. Organochlorine pesticides and PCBs in air of southern Mexico (2002-2004)

    Science.gov (United States)

    Alegria, Henry A.; Wong, Fiona; Jantunen, Liisa M.; Bidleman, Terry F.; Figueroa, Miguel Salvador; Bouchot, Gerardo Gold; Moreno, Victor Ceja; Waliszewski, Stefan M.; Infanzon, Raul

    Air samples were collected in southern Mexico in 2002-2004 to determine the extent of contamination with organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs). The ΣDDTs ranged from 239 to 2360 pg m -3. Other prominent OC pesticides were endosulfans, toxaphene and lindane. Pesticides detected in lower concentrations include chlordanes, dieldrin, and heptachlor. Proportions of DDT compounds suggested fresh use of DDT in some locations and a mix of fresh and aged residues at others. Ratios of trans-chlordane/ cis-chlordane were consistent with fresh chlordane usage or emission of residues from former termiticide applications. The ΣPCBs was relatively low at all sites. Concentrations of OC pesticides measured with passive samplers agreed well with those measured using high-volume samplers. Air back trajectory analysis suggests a complex pattern of regional atmospheric transport.

  12. Retinal dopamine mediates multiple dimensions of light-adapted vision.

    Science.gov (United States)

    Jackson, Chad R; Ruan, Guo-Xiang; Aseem, Fazila; Abey, Jane; Gamble, Karen; Stanwood, Greg; Palmiter, Richard D; Iuvone, P Michael; McMahon, Douglas G

    2012-07-04

    Dopamine is a key neuromodulator in the retina and brain that supports motor, cognitive, and visual function. Here, we developed a mouse model on a C57 background in which expression of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, is specifically disrupted in the retina. This model enabled assessment of the overall role of retinal dopamine in vision using electrophysiological (electroretinogram), psychophysical (optokinetic tracking), and pharmacological techniques. Significant disruptions were observed in high-resolution, light-adapted vision caused by specific deficits in light responses, contrast sensitivity, acuity, and circadian rhythms in this retinal dopamine-depleted mouse model. These global effects of retinal dopamine on vision are driven by the differential actions of dopamine D1 and D4 receptors on specific retinal functions and appear to be due to the ongoing bioavailability of dopamine rather than developmental effects. Together, our data indicate that dopamine is necessary for the circadian nature of light-adapted vision as well as optimal contrast detection and acuity.

  13. Solubility enhancement of dioxins and PCBs by surfactant monomers and micelles quantified with polymer depletion techniques.

    Science.gov (United States)

    Schacht, Veronika J; Grant, Sharon C; Escher, Beate I; Hawker, Darryl W; Gaus, Caroline

    2016-06-01

    Partitioning of super-hydrophobic organic contaminants (SHOCs) to dissolved or colloidal materials such as surfactants can alter their behaviour by enhancing apparent aqueous solubility. Relevant partition constants are, however, challenging to quantify with reasonable accuracy. Partition constants to colloidal surfactants can be measured by introducing a polymer (PDMS) as third phase with known PDMS-water partition constant in combination with the mass balance approach. We quantified partition constants of PCBs and PCDDs (log KOW 5.8-8.3) between water and sodium dodecyl sulphate monomers (KMO) and micelles (KMI). A refined, recently introduced swelling-based polymer loading technique allowed highly precise (4.5-10% RSD) and fast (KMO. SHOC losses to experimental surfaces were substantial (8-26%) in monomer solutions, but had a low impact on KMO (0.10-0.16 log units). Log KMO for PCDDs (4.0-5.2) were approximately 2.6 log units lower than respective log KMI, which ranged from 5.2 to 7.0 for PCDDs and 6.6-7.5 for PCBs. The linear relationship between log KMI and log KOW was consistent with more polar and moderately hydrophobic compounds. Apparent solubility increased with increasing hydrophobicity and was highest in micelle solutions. However, this solubility enhancement was also considerable in monomer solutions, up to 200 times for OCDD. Given the pervasive presence of surfactant monomers in typical field scenarios, these data suggest that low surfactant concentrations may be effective long-term facilitators for subsurface transport of SHOCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Cat retinal ganglion cell receptive-field alterations after 6-hydroxydopamine induced dopaminergic amacrine cell lesions

    International Nuclear Information System (INIS)

    Maguire, G.W.; Smith, E.L. III

    1985-01-01

    Optic tract single-unit recordings were used to study ganglion cell response functions of the intact cat eye after 6-hydroxydopamine (6-OHDA) lesioning of the dopaminergic amacrine cell (AC) population of the inner retina. The impairment of the dopaminergic AC was verified by high pressure-liquid chromatography with electrochemical detection of endogenous dopamine content and by [ 3 H]dopamine high-affinity uptake; the dopaminergic ACs of the treated eyes demonstrated reduced endogenous dopamine content and reduced [ 3 H]dopamine uptake compared with that of their matched controls. Normal appearing [ 3 H]GABA and [ 3 H]-glycine uptake in the treated retinas suggests the absence of any nonspecific action of the 6-OHDA on the neural retina. The impairment of the dopaminergic AC population was found to alter a number of response properties in off-center ganglion cells, but this impairment had only a modest effect on the on-center cells. An abnormally high proportion of the off-center ganglion cells in the 6-OHDA treated eyes possessed nonlinear, Y-type receptive fields. These cells also possessed shift-responses of greater than normal amplitude, altered intensity-response functions, reduced maintained activities, and more transient center responses. Of the on-center type cells, only the Y-type on-center cells were affected by 6-OHDA, possessing higher than normal maintained activities and altered intensity-response functions. The on-center X-cells were unaffected by 6-OHDA treatment. The dopaminergic AC of the photopically adapted cat retina therefore modulates a number of ganglion cell response properties and within the limits of this study is most prominent in off-center ganglion cell circuitry

  15. Behavioral Phenotyping of Dopamine Transporter Knockout Rats: Compulsive Traits, Motor Stereotypies, and Anhedonia

    Directory of Open Access Journals (Sweden)

    Stefano Cinque

    2018-02-01

    Full Text Available Alterations in dopamine neurotransmission are generally associated with diseases such as attention-deficit/hyperactivity disorder (ADHD and obsessive-compulsive disorder (OCD. Such diseases typically feature poor decision making and lack of control on executive functions and have been studied through the years using many animal models. Dopamine transporter (DAT knockout (KO and heterozygous (HET mice, in particular, have been widely used to study ADHD. Recently, a strain of DAT KO rats has been developed (1. Here, we provide a phenotypic characterization of reward sensitivity and compulsive choice by adult rats born from DAT–HET dams bred with DAT–HET males, in order to further validate DAT KO rats as an animal model for preclinical research. We first tested DAT KO rats’ sensitivity to rewarding stimuli, provided by highly appetitive food or sweet water; then, we tested their choice behavior with an Intolerance-to-Delay Task (IDT. During these tests, DAT KO rats appeared less sensitive to rewarding stimuli than wild-type (WT and HET rats: they also showed a prominent hyperactive behavior with a rigid choice pattern and a wide number of compulsive stereotypies. Moreover, during the IDT, we tested the effects of amphetamine (AMPH and RO-5203648, a trace amine-associated receptor 1 (TAAR1 partial agonist. AMPH accentuated impulsive behaviors in WT and HET rats, while it had no effect in DAT KO rats. Finally, we measured the levels of tyrosine hydroxylase, dopamine receptor 2 (D2, serotonin transporter, and TAAR1 mRNA transcripts in samples of ventral striatum, finding no significant differences between WT and KO genotypes. Throughout this study, DAT KO rats showed alterations in decision-making processes and in motivational states, as well as prominent motor and oral stereotypies: more studies are warranted to fully characterize and efficiently use them in preclinical research.

  16. Free and conjugated dopamine in human ventricular fluid

    International Nuclear Information System (INIS)

    Sharpless, N.S.; Thal, L.J.; Wolfson, L.I.; Tabaddor, K.; Tyce, G.M.; Waltz, J.M.

    1981-01-01

    Free dopamine and an acid hydrolyzable conjugate of dopamine were measured in human ventricular fluid specimens with a radioenzymatic assay and by high performance liquid chromatography (HPLC) with electrochemical detection. Only trace amounts of free norepinephrine and dopamine were detected in ventricular fluid from patients with movement disorders. When the ventricular fluid was hydrolyzed by heating in HClO 4 or by lyophilization in dilute HClO 4 , however, a substantial amount of free dopamine was released. Values for free plus conjugated dopamine in ventricular fluid from patients who had never taken L-DOPA ranged from 139 to 340 pg/ml when determined by HPLC and from 223 to 428 pg/ml when measured radioenzymatically. The correlation coefficient for values obtained by the two methods in the same sample of CSF was 0.94 (P<0.001). Patients who had been treated with L-DOPA had higher levels of conjugated dopamine in their ventricular CSF which correlated inversely with the time between the last dose of L-DOPA and withdrawal of the ventricular fluid. Additionally, one patient with acute cerebral trauma had elevated levels of free norepinephrine and both free and conjugated dopamine in his ventricular fluid. Conjugation may be an important inactivation pathway for released dopamine in man. (Auth.)

  17. Antagonism of presynaptic dopamine receptors by phenothiazine drug metabolites

    International Nuclear Information System (INIS)

    Nowak, J.Z.; Arbilla, S.; Langer, S.Z.; Dahl, S.G.

    1990-01-01

    Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3 H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3 H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors

  18. Atmospheric concentrations, distributions and air-soil exchange tendencies of PAHs and PCBs in a heavily industrialized area in Kocaeli, Turkey.

    Science.gov (United States)

    Cetin, Banu; Yurdakul, Sema; Keles, Melek; Celik, Isil; Ozturk, Fatma; Dogan, Cevdet

    2017-09-01

    Dilovasi is one of the heavily industrialized areas in Turkey with serious environmental problems. In this study, the atmospheric concentration of PAHs and PCBs were measured for a whole year at 23 sites. The average ambient air Σ 15 PAH and Σ 41 PCB concentrations were found as 285 ± 431 ng m -3 and 4152 ± 6072 pg m -3 , respectively. PAH concentrations increased with decreasing temperature especially in urban areas, indicating the impact of residential heating. However, PCB concentrations mostly increased with temperature probably due to enhanced volatilization from their sources. The gradient obtained for PCBs, rural air were higher in industrial-urban areas than rural sites, showing that soil was a secondary source for PAHs. Fugacity ratios of PCBs were mostly <1.0 for the whole sampling period. Although the source/sink tendency of soil for some PCBs depends on their volatility, considering the whole data, PCBs were generally deposited to soil. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The multiplicity of the D-1 dopamine receptor

    International Nuclear Information System (INIS)

    Mailman, R.B.; Klits, C.D.; Lewis, M.H.; Rollema, H.; Schulz, D.W.; Wyrick, S.

    1986-01-01

    The authors have sought to address two questions of some neuropharmacological importance in this chapter. First, they examine the nature of mechanisms by which dopamine initiates many psychopharmacological effects and, second, they study the possibility of designing highly specific drugs targeted only at a selected subpopulation of dopamine receptors. Effects of SCH23390 and haloperidol on concentrations of dopamine, DOPAC, and HVA in various rat brain regions are shown. In addition, the effects of SCH23390 on the in vivo binding of dipropyl-5, 6-ADTN are shown. Differential distribution of a dopamine sensitive adenylate cyclase and ( 3 H)-SCH23390 binding sites are examined. A model is presented of D 1 dopamine receptors in membrane, illustrating the lack of identity of some of the ( 3 H)-SCH23390 binding sites with the dopamine receptor linked to stimulation of cAMP synthesis

  20. No evidence of association between structural polymorphism at the dopamine D3 receptor locus and alcoholism in the Japanese

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Susumu; Muramatsu, Taro; Matsushita, Sachio [National Institute on Alcoholism, Kanagawa (Japan); Murayama, Masanobu [Akagi Kougen Hospital, Gunma (Japan)

    1996-07-26

    Dopaminergic systems mediate reward mechanisms and are involved in reinforcing self-administration of dependence-forming substances, including alcohol. Studies have reported that polymorphisms of the dopamine D2 receptor, whose structure and function are similar to those of the dopamine D3 receptor, increase the susceptibility to alcoholism. The observations led to the examination of the possible association between a structural polymorphism of the D3 receptor gene and alcoholism. Genotyping results, employing a PCR-RFLP method, showed no difference in allele and genotype frequencies of the D3 BalI polymorphism (Ser{sup 9}/Gly{sup 9}) between Japanese alcoholics and controls. Moreover, these frequencies were not altered in alcoholics with inactive aldehyde dehydrogenase-2 (ALDH2), a well-defined negative risk factor for alcoholism. These results strongly suggest that the dopamine D3 receptor is not associated with alcoholism. 19 refs., 1 fig., 1 tab.

  1. Levels of dioxin (PCDD/F) and PCBs in a random sample of Australian aquaculture-produced Southern Bluefin Tuna (Thunnus maccoyii)

    Energy Technology Data Exchange (ETDEWEB)

    Padula, D.; Madigan, T.; Kiermeier, A.; Daughtry, B.; Pointon, A. [South Australian Research and Development Inst. (Australia)

    2004-09-15

    To date there has been no published information available on the levels of dioxin (PCDD/F) and PCBs in Australian aquaculture-produced Southern Bluefin Tuna (Thunnus maccoyii). Southern Bluefin Tuna are commercially farmed off the coast of Port Lincoln in the state of South Australia, Australia. This paper reports the levels of dioxin (PCDD/F) and PCBs in muscle tissue samples from 11 randomly sampled aquaculture-produced Southern Bluefin Tuna collected in 2003. Little published data exists on the levels of dioxin (PCDD/F) and PCBs in Australian aquacultureproduced seafood. Wild tuna are first caught in the Great Australian Bight in South Australian waters, and are then brought back to Port Lincoln where they are ranched in sea-cages before being harvested and exported to Japan. The aim of the study was to identify pathways whereby contaminants such as dioxin (PCDD/F) and PCBs may enter the aquaculture production system. This involved undertaking a through chain analysis of the levels of dioxin (PCDD/F) and PCBs in wild caught tuna, seafloor sediment samples from the marine environment, levels in feeds and final harvested exported product. Detailed study was also undertaken on the variation of dioxin (PCDD/F) and PCBs across individual tuna carcases. This paper addresses the levels found in final harvested product. Details on levels found in other studies will be published elsewhere shortly.

  2. Alteration of striatal dopamine levels under various partial pressure of oxygen in pre-convulsive and convulsive phases in freely-moving rats.

    Science.gov (United States)

    Lavoute, Cécile; Weiss, Michel; Risso, Jean-Jacques; Rostain, Jean-Claude

    2014-02-01

    The purpose of this study was to investigate the change in the striatal dopamine (DA) level in freely-moving rat exposed to different partial pressure of oxygen (from 1 to 5 ATA). Some works have suggested that DA release by the substantia nigra pars compacta (SNc) neurons in the striatum could be disturbed by hyperbaric oxygen (HBO) exposure, altering therefore the basal ganglia activity. Such changes could result in a change in glutamatergic and GABAergic control of the dopaminergic neurons into the SNc. Such alterations could provide more information about the oxygen-induced seizures observed at 5 ATA in rat. DA-sensitive electrodes were implanted into the striatum under general anesthesia. After 1 week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 1, 2, 3, 4 and 5 ATA. DA level was monitored continuously (every 3 min) by in vivo voltammetry before and during HBO exposure. HBO induced a decrease in DA level in relationship to the increase in partial pressure of oxygen from 1 ATA to 4 ATA (-15 % at 1 ATA, -30 % at 2 ATA, -40 % at 3 ATA, -45 % at 4 ATA), without signs of oxygen toxicity. At 5 ATA, DA level strongly decreases (-75 %) before seizure which occurred after 27 min ± 7 HBO exposure. After the epileptic seizure the decrease in DA level disappeared. These changes and the biphasic effect of HBO were discussed in function of HBO action on neurochemical regulations of the nigro striatal pathway.

  3. Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human population

    Directory of Open Access Journals (Sweden)

    George J Trachte

    2009-04-01

    Full Text Available George J Trachte1, Thomas Uncini2, Marty Hinz31Department of Physiology and Pharmacology, University of MN Medical School Duluth, Duluth, MN, USA; 2Chief Medical Examiner, St. Louis County, Hibbing, MN, USA; 3Clinical Research, NeuroResearch Clinics, Inc., Duluth, MN, USA Abstract: Amino acid precursors of dopamine and serotonin have been administered for decades to treat a variety of clinical conditions including depression, anxiety, insomnia, obesity, and a host of other illnesses. Dietary administration of these amino acids is designed to increase dopamine and serotonin levels within the body, particularly the brain. Convincing evidence exists that these precursors normally elevate dopamine and serotonin levels within critical brain tissues and other organs. However, their effects on urinary excretion of neurotransmitters are described in few studies and the results appear equivocal. The purpose of this study was to define, as precisely as possible, the influence of both 5-hydroxytryptophan (5-HTP and tyrosine on urinary excretion of serotonin and dopamine in a large human population consuming both 5-HTP and tyrosine. Curiously, only 5-HTP exhibited a marginal stimulatory influence on urinary serotonin excretion when 5-HTP doses were compared to urinary serotonin excretion; however, a robust relationship was observed when alterations in 5-HTP dose were compared to alterations in urinary serotonin excretion in individual patients. The data indicate three statistically discernible components to 5-HTP responses, including inverse, direct, and no relationships between urinary serotonin excretion and 5-HTP doses. The response to tyrosine was more consistent but primarily yielded an unexpected reduction in urinary dopamine excretion. These data indicate that the urinary excretion pattern of neurotransmitters after consumption of their precursors is far more complex than previously appreciated. These data on urinary neurotransmitter excretion might

  4. PCBs Contaminantion of Transformer Oil and its Occupational Health and Safety Status in the Kathmandu Valley, Nepal

    Directory of Open Access Journals (Sweden)

    Laxman K.C.

    2014-12-01

    Full Text Available Electrification in Kathmandu valley had started in 1911 and the use of polychlorinated biphenyls (PCBs probably started since 1940s (Devkota, 2005. This research work was undertaken to find out the degree and extent of PCBs contamination in transformer oil and to explore its impacts on occupational health and safety issues of the workers and on the environment. The research was focused on Distributions Centers of the Nepal Electricity Authority (NEA in the Kathmandu valley, NEA Lainchaur workshop and welding workshops of the Kathmandu valley. The samples of transformer oil were collected, safely stored and analyzed using L2000DX Chloride Analyzer, PCBs contamination at >50 ppm level was found in 184 distribution transformers with total volume of PCBs contaminated transformer oil to be 67566.3 Kg. The knowledge on impacts of PCBs contaminated transformer oil on human health and environment was better among NEA employees than among employees of welding workshops, though not satisfactory. Due to very low awareness, the workers come in contact with the transformer oil regularly and many health impacts such as eye problems, skin related complication, weakness and respiratory problems might be due to this exposure; however, exact impacts could not be verified scientifically.DOI: http://dx.doi.org/10.3126/ije.v3i4.11727       International Journal of EnvironmentVolume-3, Issue-4, Sep-Nov 2014Page : 12-23 

  5. Increased brain dopamine and dopamine receptors in schizophrenia

    International Nuclear Information System (INIS)

    Mackay, A.V.; Iversen, L.L.; Rossor, M.; Spokes, E.; Bird, E.; Arregui, A.; Creese, I.; Synder, S.H.

    1982-01-01

    In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients

  6. Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.

    Directory of Open Access Journals (Sweden)

    Laura Dazzi

    Full Text Available Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1

  7. Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.

    Science.gov (United States)

    Dazzi, Laura; Talani, Giuseppe; Biggio, Francesca; Utzeri, Cinzia; Lallai, Valeria; Licheri, Valentina; Lutzu, Stefano; Mostallino, Maria Cristina; Secci, Pietro Paolo; Biggio, Giovanni; Sanna, Enrico

    2014-01-01

    Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this

  8. Cat serum contamination by phthalates, PCBs, and PBDEs versus food and indoor air.

    Science.gov (United States)

    Braouezec, Clélie; Enriquez, Brigitte; Blanchard, Martine; Chevreuil, Marc; Teil, Marie-Jeanne

    2016-05-01

    A wide variety of endocrine disrupting compounds (EDCs) with semi-volatile properties are emitted to indoor air and, thus, humans might get exposed to these compounds. Pet cats spend the major part of their lifetime at home and might integrate indoor contamination so that they could mirror the human exposure. Three classes of EDCs, polybromodiphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and phthalates (PAEs), were simultaneously considered and quantified in the serum of cats (Felis silvestris catus) living in the Paris area (France). The main compound concentrations by decreasing importance order were as follows: for PAEs, di-n-butyl phthalate (79,900 ng L(-1)) next di-iso-butyl phthalate (53,200 ng L(-1)), di-iso-nonyl phthalate (43,800 ng L(-1)), and di-ethylhexyl phthalate (32,830 ng L(-1)); for PCBs, CB153 (1378 ng L(-1)) next CB52 (509 ng L(-1)), CB101 (355 ng L(-1)), CB110 (264 ng L(-1)), and CB118 (165 ng L(-1)); and for PBDEs, BDE 153/154 (35 ng L(-1)) next BDE47 (10.7 ng L(-1)). Total serum concentrations as mean ± standard deviation were 107 ± 98 μg L(-1) for ∑9PAEs, 2799 ± 944 ng L(-1) for ∑19PCBs, and 56 ± 21 ng L(-1) for ∑9BDEs. The three chemical groups were found in cat food: 0.088 ng g(-1) for ∑9BDEs, 1.7 ng g(-1) for ∑19PCBs, and 2292 ng g(-1) for ∑9PAEs and in indoor air: 0.063 ng m(-3) for ∑9BDEs, 1.5 ng m(-3) for ∑19PCBs, and 848 ng m(-3) for ∑9PAEs. Contaminant intake by food ingestion was approximately 100-fold higher than that by indoor air inhalation.

  9. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    Science.gov (United States)

    Anselmi, L; Toti, L; Bove, C; Travagli, R A

    2017-11-01

    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

  10. Human dopamine receptor and its uses

    Energy Technology Data Exchange (ETDEWEB)

    Civelli, Olivier (Portland, OR); Van Tol, Hubert Henri-Marie (Toronto, CA)

    1999-01-01

    The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

  11. Radiolytic removal of PCBs from isooctane and hydraulic oil solutions

    International Nuclear Information System (INIS)

    Mincher, B.J.; Arbon, R.E.; Schwendimann, G.L.

    1995-01-01

    Research at the Idaho National Engineering Laboratory (INEL) has shown the ability to degrade PCBs by exposure to gamma radiation in a number of solvents, including hydraulic oils. Radiolysis with gamma-rays may be achieved in the absence of activation or contamination and does not result in a radiologically contaminated product. While much of the original work was done in isopropanol, recent studies have been performed in isooctane as an oil surrogate. Use of isooctane permits radiolysis studies in a surrogate reasonably similar to oils yet one in which analytical work is considerably simplified. Results in both isopropanol and isooctane show the mechanism to be one of reductive dechlorination, probably associated with electron capture of solvated electrons by the PCBs. The electrons are generated by radiolysis of the solvent. Data is presented showing rate constants for the radiolysis of individual PCB congeners, in isooctane and the decomposition of Aroclor 1260 in hydraulic oil

  12. CRYSTAL STRUCTURE OF HUMAN DOPAMINE BETA-HYDROXYLASE

    DEFF Research Database (Denmark)

    2017-01-01

    A crystalline form of dopamine β-hydroxylase is provided. X-ray crystallography reveals the space group and cell dimensions, as well as the atomic coordinates. The information can be used for identifying one or more modulators of dopamine β-hydroxylase, which can then be chemically synthesised...... and used in treatment. A process for preparing the crystalline form of human dopamine β-hydroxylase is also provided....

  13. Accumulation of PCBs and other POPs in Canada's Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Anon

    2001-02-01

    High concentrations of polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs) have been found in sea-food traditionally eaten by First Nations' people of the Arctic. Since PCBs have never been manufactured in the Arctic these high concentrations cannot be attributed to local sources; they must have been transported from other regions. Due to its cold climate, the Arctic acts a sink for contaminants such as PCBs, originating from around the world and carried by Arctic air masses. Semi-volatile compounds are carried to the Arctic by cycles of evaporation, transport and condensation. Rain, snow, ice and dry deposition capture the airborne contaminants and pollute the surface on which they settle. The contaminants are processed in rivers by sedimentation and resuspension of particles, and lakes, estuaries and deltas act as sinks. The effects of these contaminants is not fully understood, although it is clear that they accumulate in fatty tissues, thus posing special danger to First Nations people who are known to consume fatty sea mammals. Inuit adults from Arctic Quebec and Greenland have PCB concentrations in their blood seven times higher than found in North American adults; 35 times higher than Health Canada's 'level of concern' for women of reproductive age. The cleanup of all PCB and other POP sources is believed to be the only preventative solution, but agreement among countries about how to deal with the existing POPs in the environment to date has proven to be difficult.

  14. Flipped Phenyl Ring Orientations of Dopamine Binding with Human and Drosophila Dopamine Transporters: Remarkable Role of Three Nonconserved Residues.

    Science.gov (United States)

    Yuan, Yaxia; Zhu, Jun; Zhan, Chang-Guo

    2018-03-09

    Molecular modeling and molecular dynamics simulations were performed in the present study to examine the modes of dopamine binding with human and Drosophila dopamine transporters (hDAT and dDAT). The computational data revealed flipped binding orientations of dopamine in hDAT and dDAT due to the major differences in three key residues (S149, G153, and A423 of hDAT vs A117, D121, and S422 of dDAT) in the binding pocket. These three residues dictate the binding orientation of dopamine in the binding pocket, as the aromatic ring of dopamine tends to take an orientation with both the para- and meta-hydroxyl groups being close to polar residues and away from nonpolar residues of the protein. The flipped binding orientations of dopamine in hDAT and dDAT clearly demonstrate a generally valuable insight concerning how the species difference could drastically affect the protein-ligand binding modes, demonstrating that the species difference, which is a factor rarely considered in early drug design stage, must be accounted for throughout the ligand/drug design and discovery processes in general.

  15. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Science.gov (United States)

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  16. Dopamine, T cells and multiple sclerosis (MS).

    Science.gov (United States)

    Levite, Mia; Marino, Franca; Cosentino, Marco

    2017-05-01

    Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in

  17. Dopamine signaling and myopia development: What are the key challenges.

    Science.gov (United States)

    Zhou, Xiangtian; Pardue, Machelle T; Iuvone, P Michael; Qu, Jia

    2017-11-01

    In the face of an "epidemic" increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this "myopia booming" and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including retina development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Decreased spontaneous activity in AMPK alpha 2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism

    DEFF Research Database (Denmark)

    Møller, Lisbeth Liliendal Valbjørn; Sylow, Lykke; Gøtzsche, Casper René

    2016-01-01

    was tested in an open field test. Furthermore, we investigated maximal running capacity and voluntary running over a period of 19 days. AMPK α2 KD mice ran 30% less in daily distance compared to WT. Furthermore, AMPK α2 KD mice showed significantly decreased locomotor activity in the open field test compared...... through alterations of the brain dopamine levels specifically in the striatal region. To test this hypothesis, transgenic mice overexpressing an inactivatable dominant negative α2 AMPK construct (AMPK α2 KD) in muscles and littermate wildtype (WT) mice were tested. AMPK α2 KD mice have impaired running...... capacity and display reduced voluntary wheel running activity. Striatal content of dopamine and its metabolites were measured under basal physiological conditions and after cocaine-induced dopamine efflux from the ventral striatum by in vivo microdialysis. Moreover, cocaine-induced locomotor activity...

  19. 77 FR 54863 - Polychlorinated Biphenyls (PCBs): Revisions to Manifesting Regulations

    Science.gov (United States)

    2012-09-06

    ... today's rule on small entities, small entity is defined as: (1) A small business that is primarily...). Today's changes are to match, as much as possible, the manifesting requirements for PCBs under TSCA to... to be Confidential Business Information (CBI) or other information whose disclosure is restricted by...

  20. A comparison of dioxins, dibenzofurans and coplanar PCBs in uncooked and broiled ground beef, catfish and bacon.

    Science.gov (United States)

    Schecter, A; Dellarco, M; Päpke, O; Olson, J

    1998-01-01

    The primary source of dioxins (PCDDs), dibenzofurans (PCDFs) and coplanar PCBs for the general population is food, especially meat, fish, and dairy products. However, most data on the levels of these chemicals is from food in the raw or uncooked state. We report here the effect of one type of cooking (broiling) on the levels of PCDDs, PCDFs, and coplanar PCBs in ground beef (hamburger), bacon and catfish. Samples of hamburger, bacon, and catfish were broiled and compared to uncooked samples in order to measure changes in the amounts of dioxins in cooked food. The total amount of PCDD, PCDF, and coplanar PCB TEQ decreased by approximately 50% on average for each portion as a result of broiling the hamburger, bacon and catfish specimens. The mean concentration (pg TEQ/kg, wet weight) of PCDDs, PCDFs, and coplanar PCBs, however, remained the same in the hamburger, increased by 83% in the bacon, and decreased by 34% in the catfish. On average, the total measured concentration (pg/kg) of the congeners of PCDDs, PCDFs, and coplanar PCBs increased 14% in the hamburger, increased 29% in the bacon, and decreased 33% in the catfish.

  1. Dopamine D2 receptors photolabeled by iodo-azido-clebopride.

    Science.gov (United States)

    Niznik, H B; Dumbrille-Ross, A; Guan, J H; Neumeyer, J L; Seeman, P

    1985-04-19

    Iodo-azido-clebopride, a photoaffinity compound for dopamine D2 receptors, had high affinity for canine brain striatal dopamine D2 receptors with a dissociation constant (Kd) of 14 nM. Irradiation of striatal homogenate with iodo-azido-clebopride irreversibly inactivated 50% of dopamine D2 receptors at 20 nM (as indicated by subsequent [3H]spiperone binding). Dopamine agonists and antagonists prevented this photo-inactivation with the appropriate rank-order of potency. Striatal dopamine D1, serotonin (S2), alpha 1- and beta-adrenoceptors were not significantly inactivated following irradiation with iodo-azido-clebopride. Thus, iodo-azido-clebopride is a selective photoaffinity probe for dopamine D2 receptors, the radiolabelled form of which may aid in the molecular characterization of these proteins.

  2. PCBs and DDT in the serum of juvenile California sea lions: associations with vitamins A and E and thyroid hormones

    International Nuclear Information System (INIS)

    Debier, Cathy; Ylitalo, Gina M.; Weise, Michael; Gulland, Frances; Costa, Daniel P.; Le Boeuf, Burney J.; Tillesse, Tanguy de; Larondelle, Yvan

    2005-01-01

    Top-trophic predators like California sea lions bioaccumulate high levels of persistent fat-soluble pollutants that may provoke physiological impairments such as endocrine or vitamins A and E disruption. We measured circulating levels of polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) in 12 healthy juvenile California sea lions captured on An-tilde o Nuevo Island, California, in 2002. We investigated the relationship between the contamination by PCBs and DDT and the circulating levels of vitamins A and E and thyroid hormones (thyroxine, T4 and triiodothyronine, T3). Serum concentrations of total PCBsPCBs) and total DDT were 14 ± 9 mg/kg and 28 ± 19 mg/kg lipid weight, respectively. PCB toxic equivalents (ΣPCB TEQs) were 320 ± 170 ng/kg lipid weight. Concentrations of ΣPCBs and ΣPCB TEQs in serum lipids were negatively correlated (p 0.1). As juvenile California sea lions are useful sentinels of coastal contamination, the high levels encountered in their serum is cause for concern about the ecosystem health of the area. - Results show high levels of organochlorine contaminants in juvenile California sea lions and a link between vitamin A, thyroid hormones and PCB exposure

  3. ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS

    Science.gov (United States)

    Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.

    2014-01-01

    Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971

  4. Dopamine agonist withdrawal syndrome: implications for patient care.

    Science.gov (United States)

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

  5. Dopamine replacement modulates oscillatory coupling between premotor and motor cortical areas in Parkinson's disease

    DEFF Research Database (Denmark)

    Herz, Damian Marc; Florin, Esther; Christensen, Mark Schram

    2014-01-01

    PM to SMA and significantly strengthened coupling in the feedback connection from M1 to lPM expressed as β-β as well as θ-β coupling. Enhancement in cross-frequency θ-β coupling from M1 to lPM was correlated with levodopa-induced improvement in motor function. The results show that PD is associated...... with an altered neural communication between premotor and motor cortical areas, which can be modulated by dopamine replacement....

  6. Systemic effects of low-dose dopamine during administration of cytarabine.

    Science.gov (United States)

    Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

    2017-09-01

    Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

  7. PCDDs, PCDFs, and PCBs co-occurrence in TiO2 nanoparticles

    NARCIS (Netherlands)

    Ctistis, Georgios; Schön, Peter; Bakker, Wouter; Luthe, Gregor

    2016-01-01

    In the present study, we report on the co-occurrence of persistent organic pollutants (POPs) adsorbed on nanoparticular titanium dioxide (TiO2). We report on the finding of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) on the

  8. 77 FR 74006 - Polychlorinated Biphenyls (PCBs); Recycling Plastics From Shredder Residue

    Science.gov (United States)

    2012-12-12

    ... instance, because substantial automotive recycling systems are already in place for the primary purpose of... (PCBs); Recycling Plastics From Shredder Residue AGENCY: Environmental Protection Agency (EPA). ACTION... currently under consideration that would generally allow for the recycling of plastic separated from...

  9. 78 FR 20640 - Polychlorinated Biphenyls (PCBs); Recycling Plastics from Shredder Residue

    Science.gov (United States)

    2013-04-05

    ... (PCBs); Recycling Plastics from Shredder Residue AGENCY: Environmental Protection Agency (EPA). ACTION....gov or at the Office of Pollution Prevention and Toxics Docket (OPPT Docket), Environmental Protection... that would produce broad environmental benefits and increase global competitiveness (Ref. 2). ISRI...

  10. Dioxins and PCBs in feed and food--review from European perspective.

    Science.gov (United States)

    Malisch, Rainer; Kotz, Alexander

    2014-09-01

    During the 1990s, a number of adverse contamination incidents focussed the attention of the media and the general public on food safety. This led to the evaluation of safety measures with regard to dioxin intake from food. Important aspects regarding dioxins and PCBs in the food chain are reviewed here, allowing a contextual understanding of the present situation through its chronological developments. About 90-98% of the average exposure of humans to dioxins and PCBs results from dietary intake, with food of animal origin being the predominant source. Therefore, animal feed contributes considerably to the presence of these compounds in food. The detection of the "real" source of a contamination event in the food chain is a complex scientific problem and requires specific knowledge on production processes and changes of patterns during bioaccumulation. This is demonstrated by complex investigations performed in three studies on two continents to identify the source (e.g. from contamination of cow's milk in Germany, to citrus pulp pellets from Brazil as an ingredient in feed, then to contaminated lime for neutralization and finally to a landfill with residues of vinyl chloride monomer production). This example shows also the substantial economic losses resulting from incidents in the food chain and the consequences to global trade. In 2001, the EU Scientific Committee on Food established a group tolerable weekly intake (TWI) of 14 pg WHO-TEQ/kg body weight and concluded that a considerable proportion of the European population would exceed this TWI. On the global level, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) provides scientific advice to the Codex Alimentarius Commission and therefore contributes to harmonized international food standards. In its evaluation of 2001, JECFA derived a provisional tolerable monthly intake (PTMI) of 70 pg TEQ/kg body weight. The sum of the median intake of PCDD/F-TEQ and PCB-TEQ exceeded the PTMI in Western European

  11. Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.

    Science.gov (United States)

    Mor, Danielle E; Tsika, Elpida; Mazzulli, Joseph R; Gould, Neal S; Kim, Hanna; Daniels, Malcolm J; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L; Tan, Victor X; Kalb, Robert G; Caldwell, Kim A; Caldwell, Guy A; Wolfe, John H; Ischiropoulos, Harry

    2017-11-01

    Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice. In contrast, raising dopamine levels in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable Caenorhabditis elegans models, expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. These data suggest that a unique mechanism links two cardinal features of PD: dopaminergic cell death and α-synuclein aggregation.

  12. Monitoring of organic micropollutants in Ghana by combination of pellet watch with sediment analysis: e-waste as a source of PCBs.

    Science.gov (United States)

    Hosoda, Junki; Ofosu-Anim, John; Sabi, Edward Benjamin; Akita, Lailah Gifty; Onwona-Agyeman, Siaw; Yamashita, Rei; Takada, Hideshige

    2014-09-15

    Plastic resin pellets collected at 11 beaches covering the whole Ghanaian coastline were analyzed for polychlorinated biphenyls (PCBs). PCB concentrations (∑13 congeners) were higher in Accra, capital city, and Tema (39-69 ng/g-pellets) than those in rural coastal towns (1-15 ng/g-pellets) which are close to global background, indicating local inputs of PCBs. River sediments were also analyzed for PCBs together with molecular markers. Sedimentary PCBs concentrations were highest at a site (AR02) downstream of an electronic waste (e-waste) scrapyard. At the site (AR02), concentration of linear alkylbenzenes (LABs), a marker of municipal wastewater, was lower than another site (AR03) which is located at the downstream of downtown Accra. This result suggests that PCBs are introduced more to the river from the e-waste site than from activities in downtown Accra. PAHs concentrations were relatively higher in urban areas with strong petrogenic signature. Abundance of triphenylbenzenes suggested plastic combustion near e-waste scrapyard. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Regulation of Dopamine Uptake by Vasoactive Peptides in the Kidney

    Directory of Open Access Journals (Sweden)

    N. L. Rukavina Mikusic

    2016-01-01

    Full Text Available Considering the key role of renal dopamine in tubular sodium handling, we hypothesized that c-type natriuretic peptide (CNP and Ang-(1-7 may regulate renal dopamine availability in tubular cells, contributing to Na+, K+-ATPase inhibition. Present results show that CNP did not affect either 3H-dopamine uptake in renal tissue or Na+, K+-ATPase activity; meanwhile, Ang-(1-7 was able to increase 3H-dopamine uptake and decreased Na+, K+-ATPase activity in renal cortex. Ang-(1-7 and dopamine together decreased further Na+, K+-ATPase activity showing an additive effect on the sodium pump. In addition, hydrocortisone reversed Ang-(1-7-dopamine overinhibition on the enzyme, suggesting that this inhibition is closely related to Ang-(1-7 stimulation on renal dopamine uptake. Both anantin and cANP (4-23-amide did not modify CNP effects on 3H-dopamine uptake by tubular cells. The Mas receptor antagonist, A-779, blocked the increase elicited by Ang-(1-7 on 3H-dopamine uptake. The stimulatory uptake induced by Ang-(1-7 was even more pronounced in the presence of losartan, suggesting an inhibitory effect of Ang-(1-7 on AT1 receptors on 3H-dopamine uptake. By increasing dopamine bioavailability in tubular cells, Ang-(1-7 enhances Na+, K+-ATPase activity inhibition, contributing to its natriuretic and diuretic effects.

  14. Layered reward signalling through octopamine and dopamine in Drosophila.

    Science.gov (United States)

    Burke, Christopher J; Huetteroth, Wolf; Owald, David; Perisse, Emmanuel; Krashes, Michael J; Das, Gaurav; Gohl, Daryl; Silies, Marion; Certel, Sarah; Waddell, Scott

    2012-12-20

    Dopamine is synonymous with reward and motivation in mammals. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies. Instead, octopamine has historically been considered to be the signal for reward in insects. Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the α-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the β-adrenergic-like OCTβ2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.

  15. Pollution of HCHs, DDTs and PCBs in tidal flat of Hangzhou Bay 2009-2013

    Science.gov (United States)

    Zhao, Peng; Gong, Wenjie; Mao, Guohua; Li, Jige; Xu, Fenfen; Shi, Jiawei

    2016-05-01

    The concentration and distribution of three persistent organic pollutants (hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs) and polychlorinated biphenyls (PCBs)) was assessed in tidal flat sediments collected from the south bank of Hangzhou Bay, China from 2009 to 2013. Gas chromatography coupled to triple quadrupole mass spectrometry (GC-MS/MS) was used for analysis, based on United States Environmental Protection Agency methods EPA8080A, EPA8081B, and EPA3550B. The results showed that the levels of HCHs, DDTs and PCBs decreased in the order of DDTs transformer or electronic equipment in the south bank of Hangzhou Bay.

  16. 75 FR 17645 - Polychlorinated Biphenyls (PCBs); Reassessment of Use Authorizations

    Science.gov (United States)

    2010-04-07

    ... Office (DCO), EPA East Bldg., Rm. 6428, 1201 Constitution Ave., NW., Washington, DC. Attention: Docket ID... action or selective metabolism of individual congeners. Noteworthy impacts on fish, birds, and mammals... have taken or planned to take and how these measures will help to safely manage their PCBs. EPA also is...

  17. Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

    Science.gov (United States)

    2015-01-01

    In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the prefrontal cortex, NAc core and shell, and dorsomedial striatum following a single intravenous infusion of ethanol (1 g/kg). The temporal patterns of these “response ratios” differed across brain regions, possibly due to regional differences in the mechanisms underlying the decline of the dopamine signal associated with acute intravenous ethanol administration and/or to the differential effects of acute ethanol on the properties of subpopulations of midbrain dopamine neurons. This Review draws on neurochemical, physiological, and molecular studies to summarize the effects of acute ethanol administration on dopamine activity in the prefrontal cortex and striatal regions, to explore the potential reasons for the regional differences observed in the decline of ethanol-induced dopamine signals, and to suggest directions for future research. PMID:25537116

  18. Central actions of a novel and selective dopamine antagonist

    International Nuclear Information System (INIS)

    Schulz, D.W.

    1985-01-01

    Receptors for the neurotransmitter dopamine traditionally have been divided into two subgroups: the D 1 class, which is linked to the stimulation of adenylate cyclase-activity, and the D 2 class which is not. There is much evidence suggesting that it is the D 2 class which is not. There is much evidence suggesting that it is the D 2 dopamine receptor that mediates the physiological and behavioral actions of dopamine in the intact animal. However, the benzazepine SCH23390 is a dopamine antagonist which has potent behavioral actions while displaying apparent neurochemical selectivity for the D 1 class of dopamine receptors. The purpose of this dissertation was to (1) confirm and characterize this selectivity, and (2) test certain hypothesis related to possible modes of action of SCH233390. The inhibition of adenylate cyclase by SCH23390 occurred via an action at the dopamine receptor only. A radiolabeled analog of SCH23390 displayed the receptor binding properties of a specific high-affinity ligand, and regional receptor densities were highly correlated with dopamine levels. The subcellular distribution of [ 3 H]-SCH23390 binding did not correspond completely with that of dopamine-stimulated adenylate cyclase. The neurochemical potency of SCH23390 as a D 1 receptor antagonist was preserved following parental administration. A variety of dopamine agonists and antagonists displayed a high correlation between their abilities to compete for [ 3 H]-SCH23390 binding in vitro and to act at an adenylate cyclase-linked receptor. Finally, the relative affinities of dopamine and SCH23390 for both D 1 receptors and [ 3 H]-SCH23390 binding sites were comparable. It is concluded that the behavioral effects of SCH23390 are mediated by actions at D 1 dopamine receptors only, and that the physiological importance of this class of receptors should be reevaluated

  19. Levels of polychlorinated dibenzo(p)dioxins, dibenzofurans and dioxin-like PCBs in Irish farmed salmon

    Energy Technology Data Exchange (ETDEWEB)

    Gruemping, R.; Hamm, S.; Stegemann, D.; Maulshagen, A. [eurofins/GfA, Muenster (Germany)

    2004-09-15

    A recent survey published by Hites in the journal Science compared the level of organochlorine contaminants including PCBs and dioxins in farmed versus wild salmon collected from around the world. Most organochlorine substances analysed in the study show a significantly higher concentration level in farmed than in wild salmon. While dioxin and PCB levels of wild fish mainly reflect the contamination level of the environment in which the fish is grown, the dioxin and PCB concentration in farmed fish may mainly be attributed to the fish feed used. In January 2004, the Irish Sea Fisheries Board (BIM) conducted the present study on the concentration of Polychlorinated Dibenzo(p)dioxins (PCDDs), Dibenzofurans (PCDFs) and dioxinlike PCBs (WHO-PCBs) in farmed salmon from two locations in Ireland. The present study should examine whether the PCDD/F and WHO-PCB levels of Irish farmed salmon correlate to the dioxin data for farmed Atlantic salmon from other countries in Northern Europe (e.g. Scotland, Faroe Islands and Norway) presented in the study by Hites. In the Hites survey, raw salmon filets with skin on were tested. Since PCBs, dioxins and other organic pollutants are mainly bound to the fish fat, a reduction of fat content by removal of the skin was supposed to lower the amount of organic contaminants. Thus, the effect of skin removal on the dioxin and PCB levels was also examined in the present study. In addition, the influence of cooking the fish meat was investigated.

  20. Molecular Mechanisms of Dopamine Receptor Mediated Neuroprotection

    National Research Council Canada - National Science Library

    Sealfon, Stuart

    2000-01-01

    ... of the cellular changes characteristic of this process. Evidence from our laboratory and others suggest that activation of dopamine receptors can oppose the induction of apoptosis in dopamine neurons...

  1. Dopamine and dopamine receptor D1 associated with decreased social interaction.

    Science.gov (United States)

    Liu, Qiang; Shi, Jieyun; Lin, Rongfei; Wen, Tieqiao

    2017-05-01

    Deficits in social interaction are hallmarks of neurological and psychiatric disorders. However, its underlying mechanism is still unclear. Here, we show that the loss of dendritic cell factor 1 (Dcf1) in the nervous system of mice induces social interaction deficiency, autism-like behaviour, and influences social interaction via the dopamine system. Dopamine receptor D1 agonist rescues this social cognition phenotype, and improves short-term plasticity. Together, this study presents a new genetic mechanism that affects social interaction and may provide a new way to improve positive social interaction and treat autism spectrum disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Illicit dopamine transients: reconciling actions of abused drugs.

    Science.gov (United States)

    Covey, Dan P; Roitman, Mitchell F; Garris, Paul A

    2014-04-01

    Phasic increases in brain dopamine are required for cue-directed reward seeking. Although compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyperactivating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyperactivation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural rewards and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor.

    Science.gov (United States)

    Radl, Daniela Betiana; Ferraris, Jimena; Boti, Valeria; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel

    2011-03-25

    Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

  4. EFFECTS OF POLYCHLORINATED-BIPHENYLS (PCBS) AND DIOXINS ON GROWTH AND DEVELOPMENT

    NARCIS (Netherlands)

    SAUER, PJJ; HUISMAN, M; KOOPMANESSEBOOM, C; MORSE, DC; SMITSVANPROOIJE, AE; VANDEBERG, KJ; TUINSTRA, LGMT; VANDERPAAUW, CG; BOERSMA, ER; WEISGLASKUPERUS, N; LAMMERS, JHCM; KULIG, BM; BROUWER, A

    1994-01-01

    Polychlorinated biphenyls (PCBs) and dioxins are potentially toxic compounds which occur widely in the environment. Their effects on the growth and development of infants at the levels currently found in highly industrialised western countries is not well known. This Dutch multicenter study,

  5. Leeches as Sensor-bioindicators of River Contamination by PCBs

    Directory of Open Access Journals (Sweden)

    Gorzyslaw Poleszczuk

    2009-03-01

    Full Text Available The aim of the study was to evaluate the use of leeches of the genus Erpobdella as a means of assessing polychlorinated biphenyl contamination of watercourses. The River Skalice, heavily contaminated with PCBs, was selected as a model. The source of contamination was a road gravel processing factory in Rožmitál pod Třemšínem from which an estimated 1 metric ton of PCBs leaked in 1986. Levels of PCB were measured in leeches collected between 1992 to 2003 from 11 sites covering about 50 km of the river (the first sampling site upstream to the source of contamination and 10 sites downstream. The PCB indicator congeners IUPA no. 28, 52, 101, 118, 138, 153, and 180 were measured. Levels were highest at the four sampling sites nearest the source of pollution. The highest values of PCB congeners were found in 1992. PCB content decreased from 1992 to 2003 and with distance from the source. The study indicated that leeches of the genus Erpobdella are a suitable bioindicator of contamination in the surface layer of river sediments.

  6. Comparison of Passive and Active Air Sampling (PAAS) Methods for PCBs – A Pilot Study in New York City Schools

    Science.gov (United States)

    PCBs were used extensively in school building materials (caulk and lighting fixture ballasts) during the approximate period of 1950-1978. Most of the schools built nationwide during this period have not had indoor air sampling conducted for PCBs. Passive air sampling holds promi...

  7. Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Mizushima Jin

    2012-07-01

    Full Text Available Abstract Dopamine dysregulation syndrome (DDS consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD. Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

  8. Detection of dopamine neurotransmission in 'real time'

    Directory of Open Access Journals (Sweden)

    Rajendra D Badgaiyan

    2013-07-01

    Full Text Available Current imaging techniques have limited ability to detect neurotransmitters released during brain processing. It is a critical limitation because neurotransmitters have significant control over the brain activity. In this context, recent development of single-scan dynamic molecular imaging technique is important because it allows detection, mapping, and measurement of dopamine released in the brain during task performance. The technique exploits the competition between endogenously released dopamine and its receptor ligand for occupancy of receptor sites. Dopamine released during task performance is detected by dynamically measuring concentration of intravenously injected radiolabeled ligand using a positron emission tomography camera. Based on the ligand concentration, values of receptor kinetic parameters are estimated. These estimates allow detection of dopamine released in the human brain during task performance.

  9. Dopamine D1 receptor activation maintains motor coordination and balance in rats.

    Science.gov (United States)

    Avila-Luna, Alberto; Gálvez-Rosas, Arturo; Durand-Rivera, Alfredo; Ramos-Languren, Laura-Elisa; Ríos, Camilo; Arias-Montaño, José-Antonio; Bueno-Nava, Antonio

    2018-02-01

    Dopamine (DA) modulates motor coordination, and its depletion, as in Parkinson's disease, produces motor impairment. The basal ganglia, cerebellum and cerebral cortex are interconnected, have functional roles in motor coordination, and possess dopamine D 1 receptors (D 1 Rs), which are expressed at a particularly high density in the basal ganglia. In this study, we examined whether the activation of D 1 Rs modulates motor coordination and balance in the rat using a beam-walking test that has previously been used to detect motor coordination deficits. The systemic administration of the D 1 R agonist SKF-38393 at 2, 3, or 4 mg/kg did not alter the beam-walking scores, but the subsequent administration of the D 1 R antagonist SCH-23390 at 1 mg/kg did produce deficits in motor coordination, which were reversed by the full agonist SKF-82958. The co-administration of SKF-38393 and SCH-23390 did not alter the beam-walking scores compared with the control group, but significantly prevented the increase in beam-walking scores induced by SCH-23390. The effect of the D 1 R agonist to prevent and reverse the effect of the D 1 R antagonist in beam-walking scores is an indicator that the function of D 1 Rs is necessary to maintain motor coordination and balance in rats. Our results support that D 1 Rs mediate the SCH-23390-induced deficit in motor coordination.

  10. Dopamine receptors in the guinea-pig heart. A binding study

    International Nuclear Information System (INIS)

    Sandrini, M.; Benelli, A.; Baraldi, M.

    1984-01-01

    The binding of dopaminergic agonists and antagonists to guinea-pig myocardial membrane preparations was studied using 3 H-dopamine and 3 H-spiperone as radioligand. 3 H-Dopamine bound specifically to heart membranes while 3 H-spiperone did not. A Scatchard analysis of 3 H-dopamine binding showed a curvilinear plot indicating the presence of two dopamine receptor populations that we have termed high- (K/sub d/ = 1.2 nM, B/sub mx/ = 52.9 fmol/mg prot.) and low- (K/sub d/ = 11.8 nM, B/sub mx/ = 267.3 fmol/gm prot.) affinity binding sites, respectively. The charactization of the high-affinity component of 3 H-dopamine binding indicated that the binding is rapid, saturable, stereospecific, pH- and temperature-dependent, and displaced by dopaminergic agonists and antagonists known to act similarly in vivo. The finding that pretreatment with dibenamine (which has been described as an α-adrenoceptor irreversible blocker) did not affect the binding of dopamine to cardiac membrane preparations suggests that α-adrenoceptors and dopamine receptors have separate recognition sites in the heart. It is concluded that 3 H-dopamine binds to specific dopamine receptors in the heart of guinea-pigs

  11. Noncovalent Interactions between Dopamine and Regular and Defective Graphene.

    Science.gov (United States)

    Fernández, Ana C Rossi; Castellani, Norberto J

    2017-08-05

    The role of noncovalent interactions in the adsorption of biological molecules on graphene is a subject of fundamental interest regarding the use of graphene as a material for sensing and drug delivery. The adsorption of dopamine on regular graphene and graphene with monovacancies (GV) is theoretically studied within the framework of density functional theory. Several adsorption modes are considered, and notably those in which the dopamine molecule is oriented parallel or quasi-parallel to the surface are the more stable. The adsorption of dopamine on graphene implies an attractive interaction of a dispersive nature that competes with Pauli repulsion between the occupied π orbitals of the dopamine ring and the π orbitals of graphene. If dopamine adsorbs at the monovacancy in the A-B stacking mode, a hydrogen bond is produced between one of the dopamine hydroxy groups and one carbon atom around the vacancy. The electronic charge redistribution due to adsorption is consistent with an electronic drift from the graphene or GV surface to the dopamine molecule. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Neuropsychological effects of chronic low-dose exposure to polychlorinated biphenyls (PCBs: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Klett Martin

    2005-10-01

    Full Text Available Abstract Background Exposure to indoor air of private or public buildings contaminated with polychlorinated biphenyls (PCBs has raised health concerns in long-term users. This exploratory neuropsychological group study investigated the potential adverse effects of chronic low-dose exposure to specific air-borne low chlorinated PCBs on well-being and behavioral measures in adult humans. Methods Thirty employees exposed to indoor air contaminated with PCBs from elastic sealants in a school building were compared to 30 non-exposed controls matched for education and age, controlling for gender (age range 37–61 years. PCB exposure was verified by external exposure data and biological monitoring (PCB 28, 101, 138, 153, 180. Subjective complaints, learning and memory, executive function, and visual-spatial function was assessed by standardized neuropsychological testing. Since exposure status depended on the use of contaminated rooms, an objectively exposed subgroup (N = 16; PCB 28 = 0.20 μg/l; weighted exposure duration 17.9 ± 7 years was identified and compared with 16 paired controls. Results Blood analyses indicated a moderate exposure effect size (d relative to expected background exposure for total PCB (4.45 ± 2.44 μg/l; d = 0.4. A significant exposure effect was found for the low chlorinated PCBs 28 (0.28 ± 0.25 μg/l; d = 1.5 and 101 (0.07 ± 0.09 μg/l; d = 0.7. Although no neuropsychological effects exceeded the adjusted significance level, estimation statistics showed elevated effect sizes for several variables. The objectively exposed subgroup showed a trend towards increased subjective attentional and emotional complaints (tiredness and slowing of practical activities, emotional state as well as attenuated attentional performance (response shifting and alertness in a cued reaction task. Conclusion Chronic inhalation of low chlorinated PCBs that involved elevated blood levels was associated with a subtle attenuation of emotional well

  13. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  14. Effects of alkylating agents on dopamine D(3) receptors in rat brain: selective protection by dopamine.

    Science.gov (United States)

    Zhang, K; Weiss, N T; Tarazi, F I; Kula, N S; Baldessarini, R J

    1999-11-13

    Dopamine D(3) receptors are structurally highly homologous to other D(2)-like dopamine receptors, but differ from them pharmacologically. D(3) receptors are notably resistant to alkylation by 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), which readily alkylates D(2) receptors. We compared EEDQ with N-(p-isothiocyanatophenethyl)spiperone (NIPS), a selective D(2)-like receptor alkylating agent, for effects on D(3) and D(2) receptors in rat brain using autoradiographic analysis. Neither agent occluded D(3) receptors in vivo at doses that produced substantial blockade of D(2) receptors, even after catecholamine-depleting pretreatments. In vitro, however, D(3) receptors were readily alkylated by both NIPS (IC(50)=40 nM) and EEDQ (IC(50)=12 microM). These effects on D(3) sites were blocked by nM concentrations of dopamine, whereas microM concentrations were required to protect D(2) receptors from the alkylating agents. The findings are consistent with the view that alkylation of D(3) receptors in vivo is prevented by its high affinity for even minor concentrations of endogenous dopamine.

  15. Behavioral effects of pre- and postnatal exposure to a mixture of low chlorinated PCBs in rats.

    Science.gov (United States)

    Lilienthal, H; Neuf, M; Munoz, C; Winneke, G

    1990-10-01

    Polychlorinated biphenyl (PCB)-treated Wistar rats were tested on three different behavioral paradigms. Animals were pre- and postnatally exposed to a technical mixture of PCBs with a chlorine content of 42%. Exposure levels were 0, 5, or 30 mg/kg diet. These conditions did not affect the health of the dams, the litter size or weight, or the physical development of the offspring. Relative liver weights in the offspring, however, were elevated in a dose-dependent manner. Open-field ambulation, active avoidance learning, and operant conditioning on a fixed interval 30-sec schedule (FI-30-sec) were used to evaluate PCB-induced behavioral alterations. Ambulation was increased in 30-mg-treated rats at Day 22, but not at Day 120. There were more avoidance responses and intertrial responses in the 30-mg group than in both other groups. On the FI-30-sec schedule slightly more reactions were emitted by the 30-mg group during the first 10 sec of the interval than by the other animals. More pronounced, however, were the differences between groups in the temporal pattern of responses within the 30-sec interval. It is concluded that in rats PCB exposure causes consistent alterations in all of the tested activity-dependent behaviors.

  16. ORAL IBOPAMINE SUBSTITUTION IN PATIENTS WITH INTRAVENOUS DOPAMINE DEPENDENCE

    NARCIS (Netherlands)

    GIRBES, ARJ; MILNER, AR; MCCLOSKEY, BV; ZWAVELING, JH; VANVELDHUISEN, DJ; ZIJLSTRA, JG; LIE, KI

    1995-01-01

    In a prospective open study we evaluated whether intravenous dopamine infusions can be safely switched to enterally administered ibopamine in dopamine-dependent patients. Six patients defined as being clinically stable, normovolaemic, but dopamine dependent, i.e. with repeated inability to stop

  17. Dopamine hypothesis of mania

    OpenAIRE

    Cookson, John

    2014-01-01

    s­of­the­Speakers­/­Konuşmacı­leriThe discovery of dopamine and its pathwaysDopamine (DA) was first synthesized in 1910 from 3,4-dihydroxy phenyl alanine (DOPA) by Barger and Ewens at Wellcome Laboratories in London. It is a cathecholamine and in the 1940s Blaschko in Cambridge proposed that DA was a precursor in synthesis of the cat-echolamine neurotransmitters noradrenaline (norepinephrine) and adrenaline (epinephrine). In 1957 it was shown to be present in the brain with other catecholamin...

  18. Dietary exposure to dioxins and dioxin-like PCBs of Hong Kong adults: results of the first Hong Kong Total Diet Study.

    Science.gov (United States)

    Wong, Waiky W K; Yip, Yiu-chung; Choi, Koon-kay; Ho, Y Y; Xiao, Ying

    2013-01-01

    Dioxins and dioxin-like polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) covered by the Stockholm Convention on POPs. To assess the associated health risk of the Hong Kong population, the dietary exposure of the Hong Kong population and various age-gender subgroups to dioxins and dioxin-like PCBs was estimated in the first Hong Kong Total Diet Study (TDS), where food samples were collected and prepared "as consumed". A total of 142 composite food samples, mainly foods of animal origin and their products and oily food, were analysed for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxin-like PCBs by the high-resolution gas chromatograph/high-resolution mass spectrometer (HRGC/HRMS) system. Dietary exposures were estimated by combining the analytical results with the food consumption data of Hong Kong adults. The mean and 95th percentile exposures to dioxins and dioxin-like PCBs of the Hong Kong population were 21.9 and 59.7 pg toxic equivalent (TEQ) kg⁻¹ body weight (bw) month⁻¹ respectively, which amounted to 31.3% and 85.2% of the provisional tolerable monthly intake (PTMI). The main dietary source of dioxins and dioxin-like PCBs was "Fish and seafood and their products" (61.9% of the total exposure), followed by "Meat, poultry and game and their products" (20.0%) and "Mixed dishes" (6.95%). The study findings suggest that the Hong Kong population is unlikely to experience the major undesirable health effects of dioxins and dioxin-like PCBs.

  19. Extraction of Polychlorinated Biphenyls (PCBs) and Dibenzyl Disulfide from Transformer Oils using Polar Aprotic Solvents andReductive Dehalogenation of Extracted PCBs

    OpenAIRE

    Kaštánek, P. (Petr); Kaštánek, F. (František); Maléterová, Y. (Ywetta); Matějková, M. (Martina); Spáčilová, L. (Lucie); Šolcová, O. (Olga)

    2014-01-01

    Extractions of PCBs from mineral oils with polar aprotic solvents (PAS) acrylonitrile AC, dimethyl sulfoxide DMSO, dimethyl formamide DMF, N-methyl pyrrolidone NMP and propylene carbonate PC were performed in order to compare the extraction efficiencies. In a single-stage extraction performed at room temperature, the efficiencies ranged from the highest to the lowest as follows: NMP → DMF → DMSO → PC → AC. NMP exhibited the highest efficiency, around 70%. . Pyridine N-oxide was also used a...

  20. K Basin Sludge Conditioning Process Testing Partitioning of PCBs in Dissolver Solution After Neutralization/Precipitation (Caustic Adjustment)

    International Nuclear Information System (INIS)

    Schmidt, A.J.; Thornton, B.M.; Hoppe, E.W.; Mong, G.M.; Silvers, K.L.; Slate, S.O.

    1999-01-01

    The purpose of the work described in this report was to gain a better understanding of how PCB congeners present in a simulated K Basin sludge dissolver solution will partition upon neutralization and precipitation (i.e., caustic adjustment). In a previous study (Mong et al. 1998),the entire series of sludge conditioning steps (acid dissolution, filtration, and caustic adjustment) were examined during integrated testing. In the work described here, the caustic adjustment step was isolated to examine the fate of PCBs in more detail within this processing step. For this testing, solutions of dissolver simulant (containing no solids) with a known initial concentration of PCB congeners were neutralized with caustic to generate a clarified supernatant and a settled sludge phase. PCBs were quantified in each phase (including the PCBs associated with the test vessel rinsates), and material balance information was collected

  1. 5-(2-Aminopropyl)benzofuran and phenazepam demonstrate the possibility of dependence by increasing dopamine levels in the brain.

    Science.gov (United States)

    Cha, Hye Jin; Lee, Kwang-Wook; Eom, Jang-Hyeon; Kim, Young-Hoon; Shin, Jisoon; Yun, Jaesuk; Han, Kyoungmoon; Kim, Hyung Soo

    2016-10-01

    Although 5-(2-aminopropyl)benzofuran (5-APB) and 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (phenazepam) are being used as recreational drugs, research on their dependence liability or mechanisms of action is lacking. The present study aimed to evaluate the behavioral effects and dependence liability of these drugs using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques were used to assess the substance-induced alterations in synaptosome-released dopamine. While both of the tested substances elicited increases in conditioned place preference and dopamine, neither of them facilitated self-administration, suggesting that 5-APB and phenazepam have rewarding effects, rather than reinforcing effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. A photoaffinity ligand for dopamine D2 receptors: azidoclebopride.

    Science.gov (United States)

    Niznik, H B; Guan, J H; Neumeyer, J L; Seeman, P

    1985-02-01

    In order to label D2 dopamine receptors selectively and covalently by means of a photosensitive compound, azidoclebopride was synthesized directly from clebopride. The dissociation constant (KD) of clebopride for the D2 dopamine receptor (canine brain striatum) was 1.5 nM, while that for azidoclebopride was 21 nM. The affinities of both clebopride and azidoclebopride were markedly reduced in the absence of sodium chloride. In the presence of ultraviolet light, azidoclebopride inactivated D2 dopamine receptors irreversibly, as indicated by the inability of the receptors to bind [3H]spiperone. Maximal photoinactivation of about 60% of the D2 dopamine receptors occurred at 1 microM azidoclebopride; 30% of the receptors were inactivated at 80 nM azidoclebopride (pseudo-IC50). Dopamine agonists selectively protected the D2 receptors from being inactivated by azidoclebopride, the order of potency being (-)-N-n-propylnorapomorphine greater than apomorphine greater than (+/-)-6,7-dihydroxy-2-aminotetralin greater than (+)-N-n-propylnorapomorphine greater than dopamine greater than noradrenaline greater than serotonin. Similarly, dopaminergic antagonists prevented the photoinactivation of D2 receptors by azidoclebopride with the following order of potency: spiperone greater than (+)-butaclamol greater than haloperidol greater than clebopride greater than (-)-sulpiride greater than (-)-butaclamol. The degree of D2 dopamine receptor photoinduced inactivation by azidoclebopride was not significantly affected by scavengers such as p-aminobenzoic acid and dithiothreitol. Furthermore, irradiation of striatal membranes with a concentration of azidoclebopride sufficient to inactivate dopamine D2 receptors by 60% did not significantly reduce dopamine D1, serotonin (S2), benzodiazepine, alpha 1- or beta-noradrenergic receptors. This study describes the use of a novel and selective photoaffinity ligand for brain dopamine D2 receptors. The molecule, in radiolabeled form, may aid in the

  3. A Review on Polychlorinated Biphenyls (PCBs) and Polybrominated Diphenyl Ethers (PBDEs) in South Asia with a Focus on Malaysia.

    Science.gov (United States)

    Kaw, Han Yeong; Kannan, Narayanan

    Malaysia is a developing country in Southeast Asia, with rapid industrial and economic growth. Speedy population growth and aggressive consumerism in the past five decades have resulted in environmental pollution issues, including products containing polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). PCBs and PBDEs are classified as persistent organic pollutants (POPs) by the Stockholm Convention due to their persistence, bioaccumulation in the environment and toxicity to humans and wildlife. These compounds are known to cause liver dysfunction, thyroid toxicity, developmental neuro-toxicity and possibly cancer. PCBs in air, mussels, pellets, seawater, fresh water, and human breast milk samples were analyzed in Malaysia, while studies on the pollution level of PBDEs in Malaysia were conducted on mussels, soils, leachate and sediment samples. PCBs in breast milk collected from Malaysia was the highest among Asian developing countries, with mean concentration of 80 ng/g lipid weight. On the other hand, the mean concentration of PCBs in mussels collected from Malaysia recorded the second lowest, with 56 ng/g and 89 ng/g lipid weight in two studies respectively. The concentrations of PBDEs in mussels taken from Malaysia fall in the range of 0.84-16 ng/g lipid weight, which is considerably low compared to 104.5 ng/g lipid weight in Philippines and 90.59 ng/g in Korea. Nevertheless, there are limited studies on these compounds in Malaysia, particularly there is no research on PBDEs in breast milk and sediment samples. This review will summarize the contamination levels of PCBs and PBDEs in different samples collected from Asian countries since 1988 until 2010 with a focus on Malaysia and will provide needed information for further research in this field.

  4. Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels.

    Science.gov (United States)

    Milienne-Petiot, Morgane; Groenink, Lucianne; Minassian, Arpi; Young, Jared W

    2017-10-01

    Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D 1 -family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D 1 -family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D 1 -family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D 1 -family receptors supports the hypothesis that D 1 and/or D 5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.

  5. Bioleaching of gold, copper and nickel from waste cellular phone PCBs and computer goldfinger motherboards by two Aspergillus nigerstrains

    Directory of Open Access Journals (Sweden)

    Jorge Enrique Madrigal-Arias

    2015-09-01

    Full Text Available In an effort to develop alternate techniques to recover metals from waste electrical and electronic equipment (WEEE, this research evaluated the bioleaching efficiency of gold (Au, copper (Cu and nickel (Ni by two strains of Aspergillus niger in the presence of gold-plated finger integrated circuits found in computer motherboards (GFICMs and cellular phone printed circuit boards (PCBs. These three metals were analyzed for their commercial value and their diverse applications in the industry. Au-bioleaching ranged from 42 to 1% for Aspergillus niger strain MXPE6; with the combination of Aspergillus niger MXPE6 + Aspergillus niger MX7, the Au-bioleaching was 87 and 28% for PCBs and GFICMs, respectively. In contrast, the bioleaching of Cu by Aspergillus niger MXPE6 was 24 and 5%; using the combination of both strains, the values were 0.2 and 29% for PCBs and GFICMs, respectively. Fungal Ni-leaching was only found for PCBs, but with no significant differences among treatments. Improvement of the metal recovery efficiency by means of fungal metabolism is also discussed.

  6. Bioleaching of gold, copper and nickel from waste cellular phone PCBs and computer goldfinger motherboards by two Aspergillus nigerstrains.

    Science.gov (United States)

    Madrigal-Arias, Jorge Enrique; Argumedo-Delira, Rosalba; Alarcón, Alejandro; Mendoza-López, Ma Remedios; García-Barradas, Oscar; Cruz-Sánchez, Jesús Samuel; Ferrera-Cerrato, Ronald; Jiménez-Fernández, Maribel

    2015-01-01

    In an effort to develop alternate techniques to recover metals from waste electrical and electronic equipment (WEEE), this research evaluated the bioleaching efficiency of gold (Au), copper (Cu) and nickel (Ni) by two strains of Aspergillus niger in the presence of gold-plated finger integrated circuits found in computer motherboards (GFICMs) and cellular phone printed circuit boards (PCBs). These three metals were analyzed for their commercial value and their diverse applications in the industry. Au-bioleaching ranged from 42 to 1% for Aspergillus niger strain MXPE6; with the combination of Aspergillus niger MXPE6 + Aspergillus niger MX7, the Au-bioleaching was 87 and 28% for PCBs and GFICMs, respectively. In contrast, the bioleaching of Cu by Aspergillus niger MXPE6 was 24 and 5%; using the combination of both strains, the values were 0.2 and 29% for PCBs and GFICMs, respectively. Fungal Ni-leaching was only found for PCBs, but with no significant differences among treatments. Improvement of the metal recovery efficiency by means of fungal metabolism is also discussed.

  7. Characteristics, distribution and sources of polychlorinated biphenyls (PCBs) in coastal sediments from the heavily industrialized area of Asalouyeh, Iran.

    Science.gov (United States)

    Arfaeinia, Hossein; Asadgol, Zahra; Ahmadi, Ehsan; Seifi, Morteza; Moradi, Masoud; Dobaradaran, Sina

    2017-12-01

    In this research, the levels of polychlorinated biphenyls (PCBs) were investigated in the marine sediments of Asaluyeh harbor, in the Persian Gulf. The samples were taken from industrial, semi-industrial and urban regions. The mean concentration levels of total (Σ) 18 detected PCBs were 514.32, 144.67 and 31.6 pg/g dw for the industrial, semi-industrial and urban sampling stations, respectively. Based on a multivariate statistical analysis, it was found that high contamination levels of PCBs in sediments collected along the Persian Gulf were associated with releases from local industries. Total organic carbon (TOC) content was significantly and positively correlated with the concentrations of PCB congeners. World Health Organization toxic equivalents (TEQs) for PCBs ranged from 0.04 to 2.66 pg TEQ/g dry weight (dw) in the coastal sediments. The TEQ values in this study were higher than many reported worldwide in the literature for sediments. This suggests that there are high levels of contamination in the area due to industrial and other human activities.

  8. PBDEs, PCBs, and DDE in eggs and their impacts on aplomado falcons (Falco femoralis) from Chihuahua and Veracruz, Mexico.

    Science.gov (United States)

    Mora, M A; Baxter, C; Sericano, J L; Montoya, A B; Gallardo, J C; Rodríguez-Salazar, J R

    2011-12-01

    Eggs from aplomado falcons (Falco femoralis septentrionalis) nesting in Chihuahua and Veracruz, Mexico, were analyzed for organochlorine pesticides, PCBs, and PBDEs. p,p'-DDE was the only organochlorine found in all eggs at concentrations ranging from 0.13 to 7.85 μg/g wet weight. PCBs ranged from 0.04 to 2.80 μg/g wet weight and PBDEs from 62 to 798 ng/g lipid weight. DDE concentrations in eggs were not significantly different among regions; however, PCBs were significantly greater (P = 0.015) in Tinaja Verde, Chihuahua than in the other three regions. Also, PBDEs were significantly higher (P Mexico. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Multiple mechanisms of PCB neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.O.; Stoner, C.T.; Lawrence, D.A. [Univ. of New York, Albany, NY (United States)] [and others

    1996-12-31

    Polychlorinated biphenyls (PCBs) have been implicated in cancer, but many of the symptoms in humans exposed to PCBs are related to the nervous system and behavior. We demonstrated three different direct mechanisms whereby PCBs are neurotoxic in rats. By using flow cytometry, we demonstrated that the orthosubstituted PCB congener 2,4,4{prime}, but neither TCDD nor the coplanar PCB congener 3,4,5,3{prime},4{prime}, causes rapid death of cerebellar granule cells. The ortho-substituted congener 2,4,4{prime} reduced long-term potentiation, an indicator of cognitive potential, in hippocampal brain slices, but a similar effect was observed for the coplanar congener 3,4,3{prime},4{prime}, indicating that this effect may be caused by both ortho- and coplanar congeners by mechanisms presumably not mediated via the Ah receptor. It was previously shown that some ortho-substituted PCB congeners cause a reduction in levels of the neurotransmitter dopamine, and we present in vitro and in vivo evidence that this is due to reduction of synthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Thus, PCBs have a variety of mechanisms of primary neurotoxicity, and neurotoxicity is a characteristic of ortho-substituted, non-dioxin-like congeners as well as some coplanar congeners. The relative contribution of each of these mechanisms to the loss of cognitive function in humans exposed to PCBs remains to be determined. 42 refs., 3 figs., 1 tab.

  10. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  11. CATALYTIC STEAM REFORMING OF CHLOROCARBONS: POLYCHLORINATED BIPHENYLS (PCBS). (R826694C633)

    Science.gov (United States)

    Experiments with commercial askarals (Aroclors 1221, 1248 and 1254) have confirmed the feasibility of catalytic steam reforming as a method for destroying polychlorinated biphenyls (PCBs). Rhodium, platinum and nickel supported on Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia.

    Science.gov (United States)

    Calcagno, B; Eyles, D; van Alphen, B; van Swinderen, B

    2013-01-08

    It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.

  12. ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS

    OpenAIRE

    Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.

    2014-01-01

    Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abuse...

  13. A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2.

    Science.gov (United States)

    Cormier, J N; Hurst, R; Vasselli, J; Lee, D; Kim, C J; McKee, M; Venzon, D; White, D; Marincola, F M; Rosenberg, S A

    1997-07-01

    The administration of high-dose interleukin-2 (IL-2) causes tumor regression in 17-25% of patients with metastatic melanoma or renal cell carcinoma. Renal dysfunction is a common dose-limiting toxicity of IL-2 administration, limiting 26% of treatment cycles. We have conducted a prospective randomized trial to evaluate whether the prophylactic administration of low-dose dopamine (2 mg/kg/min) can minimize renal toxicity and thus affect the amount of IL-2 administered. Forty-two patients were randomly assigned to receive systemic high-dose IL-2 with standard supportive measures (group A = 21 patients) or with the addition of prophylactic dopamine (group B = 21 patients) at 2 mg/kg/min. For patients in group B, dopamine was instituted 1 h before the initiation of IL-2 administration and was discontinued 6-12 h after the maximum number of doses of IL-2 were given. There was no difference in the amount of IL-2 administered for each course of therapy for groups A and B. Despite differences in urine flow (milliliters per kilogram per day), fluid balance (liters per day), and overall weight gain, prophylactic low-dose dopamine did not significantly alter maximum plasma urea or creatinine levels in group B when compared with the control group (group A). The overall toxicity profile considering all grade 3 and 4 toxicities for patients in groups A and B was comparable. Thus, there is no evidence to support the routine use of prophylactic low-dose dopamine in patients receiving high-dose IL-2.

  14. Enhanced striatal dopamine release during food stimulation in binge eating disorder

    Energy Technology Data Exchange (ETDEWEB)

    Wang, g.j.; Wang, G.-J.; Geliebter, A.; Volkow, N.D.; Telang, F.W.; Logan, Jaynbe, M.C.; Galanti, K.; Selig, P.A.; Han, H.; Zhu, W.; Wong, C.T.; Fowler, J.S.

    2011-01-13

    Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [{sup 11}C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating.

  15. Enhanced striatal dopamine release during food stimulation in binge eating disorder

    International Nuclear Information System (INIS)

    Wang, G.-J.; Geliebter, A.; Volkow, N.D.; Telang, F.W.; Logan, J.; Jaynbe, M.C.; Galanti, K.; Selig, P.A.; Han, H.; Zhu, W.; Wong, C.T.; Fowler, J.S.

    2011-01-01

    Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [ 11 C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating.

  16. Dopamine Neurons Change the Type of Excitability in Response to Stimuli

    Science.gov (United States)

    Gutkin, Boris S.; Lapish, Christopher C.; Kuznetsov, Alexey

    2016-01-01

    The dynamics of neuronal excitability determine the neuron’s response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents. Furthermore, we analyzed how excitability type of the DA neuron model is influenced by changes in the intrinsic current composition. A subthreshold sodium current is necessary for a continuous frequency decrease during application of a negative current, and the low-frequency “balanced” state during simultaneous activation of NMDA and GABA receptors. Blocking this current switches the neuron to type II characterized by the abrupt onset of repetitive firing. Enhancing the anomalous rectifier Ih current also switches the excitability to type II. Key characteristics of synaptic conductances that may be observed in vivo also change the type of excitability: a depolarized γ-Aminobutyric acid receptor (GABAR) reversal potential or co-activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) leads to an abrupt frequency drop to zero, which is typical for type II excitability. Coactivation of N-methyl-D-aspartate receptors (NMDARs) together with AMPARs and GABARs shifts the type I/II boundary toward more hyperpolarized GABAR reversal potentials. To better understand how altering each of the aforementioned currents leads to changes in excitability profile of DA neuron, we provide a thorough dynamical analysis. Collectively, these results imply that type I

  17. Administration of secretin for autism alters dopamine metabolism in the central nervous system.

    Science.gov (United States)

    Toda, Yoshihiro; Mori, Kenji; Hashimoto, Toshiaki; Miyazaki, Masahito; Nozaki, Satoshi; Watanabe, Yasuyoshi; Kuroda, Yasuhiro; Kagami, Shoji

    2006-03-01

    We evaluated the clinical effects of intravenously administered secretin in 12 children with autism (age range: 4-6 years, median age: 9 years, boy:girl=8:4). In addition, we investigated the association between improvement in symptoms and changes in the cerebrospinal fluid (CSF) homovanillic acid (HVA),5-hydroxyindole-3-acetic acid (5-HIAA), and 6R-5,6,7,8-tetrahydro-L-biopterin (BH(4)) levels after administration. After administration of secretin, the Autism Diagnostic Interview-Revised (ADI-R) score improved in 7 of the 12 children. However, the score deteriorated in 2 of the 12 children (in the item of 'restricted and repetitive, stereotyped interests and behaviors'). The HVA and BH(4) levels in CSF were increased in all children with improvement in the ADI-R score. In contrast, no patient without the elevation of the BH(4) level showed improvement in the score. These findings suggest that secretin activated metabolic turnover of dopamine in the central nervous system via BH(4), improving symptoms.

  18. Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene

    Directory of Open Access Journals (Sweden)

    Valentina Vengeliene

    2017-04-01

    Full Text Available The research domain criteria (RDoC matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here, we used a new genetic rat model with a loss-of-function point mutation in the dopamine transporter (DAT gene (Slc6a3_N157K to systematically study the RDoC matrix. First, we examined the impact of the Slc6a3_N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains: negative and positive valence systems, cognitive, social and arousal/regulatory systems. The use of RDoC may be particularly helpful for drug development. We studied the effects of a novel pharmacological approach metabotropic glutamate receptor mGluR2/3 antagonism, in DAT mutants in a comparative way with standard medications. Loss of DAT functionality in mutant rats not only elevated subcortical extracellular dopamine concentration but also altered the balance of monoaminergic transmission. DAT mutant rats showed deficits in all five RDoC domains. Thus, mutant rats failed to show conditioned fear responses, were anhedonic, were unable to learn stimulus-reward associations, showed impaired cognition and social behavior, and were hyperactive. Hyperactivity in mutant rats was reduced by amphetamine and atomoxetine, which are well-established medications to reduce hyperactivity in humans. The mGluR2/3 antagonist LY341495 also normalized hyperactivity in DAT mutant rats without affecting extracellular dopamine levels. We systematically characterized an altered dopamine system within the context of the RDoC matrix and studied mGluR2/3 antagonism as a new pharmacological strategy to treat mental disorders with underlying subcortical dopaminergic hyperactivity.

  19. Dioxins and PCBs in feed and food — Review from European perspective

    International Nuclear Information System (INIS)

    Malisch, Rainer; Kotz, Alexander

    2014-01-01

    During the 1990s, a number of adverse contamination incidents focussed the attention of the media and the general public on food safety. This led to the evaluation of safety measures with regard to dioxin intake from food. Important aspects regarding dioxins and PCBs in the food chain are reviewed here, allowing a contextual understanding of the present situation through its chronological developments. About 90–98% of the average exposure of humans to dioxins and PCBs results from dietary intake, with food of animal origin being the predominant source. Therefore, animal feed contributes considerably to the presence of these compounds in food. The detection of the “real” source of a contamination event in the food chain is a complex scientific problem and requires specific knowledge on production processes and changes of patterns during bioaccumulation. This is demonstrated by complex investigations performed in three studies on two continents to identify the source (e.g. from contamination of cow's milk in Germany, to citrus pulp pellets from Brazil as an ingredient in feed, then to contaminated lime for neutralization and finally to a landfill with residues of vinyl chloride monomer production). This example shows also the substantial economic losses resulting from incidents in the food chain and the consequences to global trade. In 2001, the EU Scientific Committee on Food established a group tolerable weekly intake (TWI) of 14 pg WHO-TEQ/kg body weight and concluded that a considerable proportion of the European population would exceed this TWI. On the global level, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) provides scientific advice to the Codex Alimentarius Commission and therefore contributes to harmonized international food standards. In its evaluation of 2001, JECFA derived a provisional tolerable monthly intake (PTMI) of 70 pg TEQ/kg body weight. The sum of the median intake of PCDD/F-TEQ and PCB-TEQ exceeded the PTMI in

  1. Dioxins and PCBs in feed and food — Review from European perspective

    Energy Technology Data Exchange (ETDEWEB)

    Malisch, Rainer, E-mail: rainer.malisch@cvuafr.bwl.de; Kotz, Alexander

    2014-09-01

    During the 1990s, a number of adverse contamination incidents focussed the attention of the media and the general public on food safety. This led to the evaluation of safety measures with regard to dioxin intake from food. Important aspects regarding dioxins and PCBs in the food chain are reviewed here, allowing a contextual understanding of the present situation through its chronological developments. About 90–98% of the average exposure of humans to dioxins and PCBs results from dietary intake, with food of animal origin being the predominant source. Therefore, animal feed contributes considerably to the presence of these compounds in food. The detection of the “real” source of a contamination event in the food chain is a complex scientific problem and requires specific knowledge on production processes and changes of patterns during bioaccumulation. This is demonstrated by complex investigations performed in three studies on two continents to identify the source (e.g. from contamination of cow's milk in Germany, to citrus pulp pellets from Brazil as an ingredient in feed, then to contaminated lime for neutralization and finally to a landfill with residues of vinyl chloride monomer production). This example shows also the substantial economic losses resulting from incidents in the food chain and the consequences to global trade. In 2001, the EU Scientific Committee on Food established a group tolerable weekly intake (TWI) of 14 pg WHO-TEQ/kg body weight and concluded that a considerable proportion of the European population would exceed this TWI. On the global level, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) provides scientific advice to the Codex Alimentarius Commission and therefore contributes to harmonized international food standards. In its evaluation of 2001, JECFA derived a provisional tolerable monthly intake (PTMI) of 70 pg TEQ/kg body weight. The sum of the median intake of PCDD/F-TEQ and PCB-TEQ exceeded the PTMI in

  2. Dopamine and glucose, obesity and Reward Deficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Kenneth eBlum

    2014-09-01

    Full Text Available Obesity and many well described eating disorders are accurately considered a global epidemic. The consequences of Reward Deficiency Syndrome, a genetic and epigenetic phenomena that involves the interactions of powerful neurotransmitters, are impairments of brain reward circuitry, hypodopaminergic function and abnormal craving behavior. Numerous sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Important facts which could translate to potential therapeutic targets espoused in this review include: 1 brain dopamine (DA production and use is stimulated by consumption of alcohol in large quantities or carbohydrates bingeing; 2 in the mesolimbic system the enkephalinergic neurons are in close proximity, to glucose receptors; 3 highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; 4 blood glucose and cerebrospinal fluid concentrations of homovanillic acid, the dopamine metabolite, are significantly correlated and 5 2-deoxyglucose the glucose analogue, in pharmacological doses associates with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and human fMRI support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and DA-modulated reward circuits are involved in pathologic eating behaviors. Treatment for addiction to glucose and drugs alike, based on a consensus of neuroscience research, should incorporate dopamine agonist therapy, in contrast to current theories and practices that use dopamine antagonists. Until now, powerful dopamine-D2 agonists have failed clinically, due to chronic down regulation of D2 receptors instead, consideration of novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of

  3. Levels of polychlorinated biphenyls (PCBs and three organochlorine pesticides in fish from the Aleutian Islands of Alaska.

    Directory of Open Access Journals (Sweden)

    Sara Hardell

    2010-08-01

    Full Text Available Persistent organic pollutants (POPs, including polychlorinated biphenyls (PCBs and chlorinated pesticides, have been shown to have many adverse human health effects. These contaminants therefore may pose a risk to Alaska Natives that follow a traditional diet high in marine mammals and fish, in which POPs bioaccumulate.This study examined the levels of PCBs and three pesticides [p, p'-DDE, mirex, and hexachlorobenzene (HCB] in muscle tissue from nine fish species from several locations around the Aleutian Islands of Alaska. The highest median PCB level was found in rock sole (Lepidopsetta bilineata, 285 ppb, wet weight, while the lowest level was found in rock greenling (Hexagrammos lagocephalus, 104 ppb, wet weight. Lipid adjusted PCB values were also calculated and significant interspecies differences were found. Again, rock sole had the highest level (68,536 ppb, lipid weight. Concerning the PCB congener patterns, the more highly chlorinated congeners were most common as would be expected due to their greater persistence. Among the pesticides, p, p'-DDE generally dominated, and the highest level was found in sockeye salmon (Oncorhynchus nerka, 6.9 ppb, wet weight. The methodology developed by U.S. Environmental Protection Agency (USEPA was used to calculate risk-based consumption limits for the analyzed fish species. For cancer health endpoints for PCBs, all species would trigger strict advisories of between two and six meals per year, depending upon species. For noncancer effects by PCBs, advisories of between seven and twenty-two meals per year were triggered. None of the pesticides triggered consumption limits.The fish analyzed, mainly from Adak, contain significant concentrations of POPs, in particular PCBs, which raises the question whether these fish are safe to eat, particularly for sensitive populations. However when assessing any risk of the traditional diet, one must also consider the many health and cultural benefits from eating

  4. PCBs, liver lesions, and biomarker responses in adult walleye (Stizostedium vitreum vitreum) collected from Green Bay, Wisconsin

    Science.gov (United States)

    Barron, Mace G.; Anderson, Michael J.; Cacela, Dave; Lipton, Joshua; Teh, Swee J.; Hinton, David E.; Zelikoff, Judith T.; Dikkeboom, Audrey L.; Tillitt, Donald E.; Holey, Mark; Denslow, Nancy

    2000-01-01

    Adult walleye were collected from several locations in the Lower Fox River and Green Bay, Wisconsin (the assessment area) and two relatively uncontaminated reference locations (Lake Winnebago and Patten Lake, Wisconsin) between July and October in 1996 and 1997. Whole body and liver samples collected in 1996 were analyzed for total PCBs, PCB congeners, and liver histological lesions. Follow-up sampling in 1997 included examination of liver histopathology, PCBs in liver samples, measurement of ethoxyresorufin-O-deethylase (EROD) activity, immunological evaluation of kidney and blood samples, measurement of plasma vitellogenin, and examination of tissues for parasites as well as bacterial and viral infections. Mean PCB concentrations in whole body and liver samples were elevated in assessment area walleye (4.6 to 8.6 and 3.6 to 6.4 mg/kg wet weight, respectively) compared to PCB concentrations in reference areas (0.04 mg/kg in walleye fillets from Lake Winnebago). A significant (p blood monocyte counts were 40% lower than those of reference area fish. The data did not show any clear distinctions in the prevalence of disease between reference and assessment area walleye. EROD activity was similar in assessment area and reference area walleye. Plasma vitellogenin was elevated in female walleye from eastern Green Bay, but was not detected in male fish from this location. The results of this investigation demonstrate significant elevation in hepatic preneoplastic lesions and hepatocellular adenomas and carcinomas in assessment area walleye exposed to elevated concentrations of PCBs. These histopathological lesions are consistent with long-term exposure to tumor promoters such as PCBs, although quantitative association between tumors and PCBs was not observed at the level of the individual fish. Additional research would be needed to elucidate the causal mechanisms underlying tumorigenesis.

  5. Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

    Science.gov (United States)

    Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

    2013-01-01

    Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

  6. Contrast Enhancement Method Based on Gray and Its Distance Double-Weighting Histogram Equalization for 3D CT Images of PCBs

    Directory of Open Access Journals (Sweden)

    Lei Zeng

    2016-01-01

    Full Text Available Cone beam computed tomography (CBCT is a new detection method for 3D nondestructive testing of printed circuit boards (PCBs. However, the obtained 3D image of PCBs exhibits low contrast because of several factors, such as the occurrence of metal artifacts and beam hardening, during the process of CBCT imaging. Histogram equalization (HE algorithms cannot effectively extend the gray difference between a substrate and a metal in 3D CT images of PCBs, and the reinforcing effects are insignificant. To address this shortcoming, this study proposes an image enhancement algorithm based on gray and its distance double-weighting HE. Considering the characteristics of 3D CT images of PCBs, the proposed algorithm uses gray and its distance double-weighting strategy to change the form of the original image histogram distribution, suppresses the grayscale of a nonmetallic substrate, and expands the grayscale of wires and other metals. The proposed algorithm also enhances the gray difference between a substrate and a metal and highlights metallic materials. The proposed algorithm can enhance the gray value of wires and other metals in 3D CT images of PCBs. It applies enhancement strategies of changing gray and its distance double-weighting mechanism to adapt to this particular purpose. The flexibility and advantages of the proposed algorithm are confirmed by analyses and experimental results.

  7. Evidence that central dopamine receptors modulate sympathetic neuronal activity to the adrenal medulla to alter glucoregulatory mechanisms.

    Science.gov (United States)

    Arnerić, S P; Chow, S A; Bhatnagar, R K; Webb, R L; Fischer, L J; Long, J P

    1984-02-01

    Previous reports suggest that analogs of dopamine (DA) can produce hyperglycemia in rats by interacting with DA receptors. Experiments reported here indicate the site of action and describe the metabolic sequalae associated with the hyperglycemic effect of apomorphine (APO), produced in conscious unrestrained rats. Apomorphine was more potent when administered by intracerebroventricular (i.c.v.) injection than when given subcutaneously (s.c.). Very small doses of the DA receptor antagonist pimozide, given intraventricularly, blocked the hyperglycemic effect of apomorphine administered subcutaneously. Sectioning of the spinal cord at thoracic vertebra T1-2 or sectioning the greater splanchnic nerve blocked apomorphine-induced hyperglycemia; whereas section of the superior colliculus or section at T5-6 had no effect. A dose of apomorphine or epinephrine (EPI) producing a similar degree of hyperglycemia elevated the concentration of EPI in serum to a similar degree, and the increase in EPI in serum preceded the increase in glucose in serum. Fasting animals for 2 or 18 hr had no significant effect on EPI- or apomorphine-induced hyperglycemia despite a reduction (91-93%) of the glycogen content of liver and skeletal muscle during the 18 hr fast. 5-Methoxyindole-2-carboxylic acid (MICA), an inhibitor of gluconeogenesis, blocked EPI- and apomorphine-induced hyperglycemia in rats fasted for 18 hr. However, 5-methoxyindole-2-carboxylic acid was ineffective in blocking hyperglycemia in animals fasted for 2 hr. Changes in insulin or glucagon in serum alone cannot account for the hyperglycemic action of apomorphine. These data demonstrate that apomorphine interacts with central DA receptors located in the hindbrain to activate sympathetic neuronal activity to the adrenal gland which subsequently releases epinephrine to alter homeostasis of glucose. Epinephrine may then, depending on the nutritional status, facilitate glycogenolytic or gluconeogenic processes to produce

  8. Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra

    International Nuclear Information System (INIS)

    Dawson, T.M.; Dawson, V.L.; Gage, F.H.; Fisher, L.J.; Hunt, M.A.; Wamsley, J.K.

    1991-01-01

    Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative [3H]BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of [3H]SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in the number (Bmax) of [3H]sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of [3H]BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat

  9. Poly(dopamine) coating to biodegradable polymers for bone tissue engineering.

    Science.gov (United States)

    Tsai, Wei-Bor; Chen, Wen-Tung; Chien, Hsiu-Wen; Kuo, Wei-Hsuan; Wang, Meng-Jiy

    2014-02-01

    In this study, a technique based on poly(dopamine) deposition to promote cell adhesion was investigated for the application in bone tissue engineering. The adhesion and proliferation of rat osteoblasts were evaluated on poly(dopamine)-coated biodegradable polymer films, such as polycaprolactone, poly(l-lactide) and poly(lactic-co-glycolic acid), which are commonly used biodegradable polymers in tissue engineering. Cell adhesion was significantly increased to a plateau by merely 15 s of dopamine incubation, 2.2-4.0-folds of increase compared to the corresponding untreated substrates. Cell proliferation was also greatly enhanced by poly(dopamine) deposition, indicated by shortened cell doubling time. Mineralization was also increased on the poly(dopamine)-deposited surfaces. The potential of poly(dopamine) deposition in bone tissue engineering is demonstrated in this study.

  10. Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Schmauss Claudia

    2007-01-01

    Full Text Available Abstract Background In both schizophrenia and addiction, pathological changes in dopamine release appear to induce alterations in the circuitry of the nucleus accumbens that affect coordinated thought and motivation. Dopamine acts principally on medium-spiny GABA neurons, which comprise 95% of accumbens neurons and give rise to the majority of inhibitory synapses in the nucleus. To examine dopamine action at single medium-spiny neuron synapses, we imaged Ca2+ levels in their presynaptic varicosities in the acute brain slice using two-photon microscopy. Results Presynaptic Ca2+ rises were differentially modulated by dopamine. The D1/D5 selective agonist SKF81297 was exclusively facilitatory. The D2/D3 selective agonist quinpirole was predominantly inhibitory, but in some instances it was facilitatory. Studies using D2 and D3 receptor knockout mice revealed that quinpirole inhibition was either D2 or D3 receptor-mediated, while facilitation was mainly D3 receptor-mediated. Subsets of varicosities responded to both D1 and D2 agonists, showing that there was significant co-expression of these receptor families in single medium-spiny neurons. Neighboring presynaptic varicosities showed strikingly heterogeneous responses to DA agonists, suggesting that DA receptors may be differentially trafficked to individual varicosities on the same medium-spiny neuron axon. Conclusion Dopamine receptors are present on the presynaptic varicosities of medium-spiny neurons, where they potently control GABAergic synaptic transmission. While there is significant coexpression of D1 and D2 family dopamine receptors in individual neurons, at the subcellular level, these receptors appear to be heterogeneously distributed, potentially explaining the considerable controversy regarding dopamine action in the striatum, and in particular the degree of dopamine receptor segregation on these neurons. Assuming that post-receptor signaling is restricted to the microdomains of

  11. Demonstration of conjugated dopamine in monkey CSF by gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Elchisak, M A; Powers, K H; Ebert, M H

    1982-09-01

    A method for measuring unconjugated and conjugated dopamine in body tissues and fluids is described. Conjugated dopamine was hydrolyzed in acid to unconjugated dopamine, separated from the sample matrix by alumina chromatography, and assayed by gas chromatography-mass spectrometry. Conjugated dopamine was detected in greater concentrations than unconjugated dopamine in CSF taken from lateral ventricle or thecal sac of the Rhesus monkey. Haloperidol administration did not increase the levels of conjugated dopamine in lumbar CSF.

  12. Phasic dopamine release drives rapid activation of striatal D2-receptors

    Science.gov (United States)

    Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

    2014-01-01

    Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

  13. Photoaffinity ligand for dopamine D2 receptors: azidoclebopride

    International Nuclear Information System (INIS)

    Niznik, H.B.; Guan, J.H.; Neumeyer, J.L.; Seeman, P.

    1985-01-01

    In order to label D2 dopamine receptors selectively and covalently by means of a photosensitive compound, azidoclebopride was synthesized directly from clebopride. The dissociation constant (KD) of clebopride for the D2 dopamine receptor (canine brain striatum) was 1.5 nM, while that for azidoclebopride was 21 nM. The affinities of both clebopride and azidoclebopride were markedly reduced in the absence of sodium chloride. In the presence of ultraviolet light, azidoclebopride inactivated D2 dopamine receptors irreversibly, as indicated by the inability of the receptors to bind [ 3 H]spiperone. Maximal photoinactivation of about 60% of the D2 dopamine receptors occurred at 1 microM azidoclebopride; 30% of the receptors were inactivated at 80 nM azidoclebopride (pseudo-IC50). Dopamine agonists selectively protected the D2 receptors from being inactivated by azidoclebopride, the order of potency being (-)-N-n-propylnorapomorphine greater than apomorphine greater than (+/-)-6,7-dihydroxy-2-aminotetralin greater than (+)-N-n-propylnorapomorphine greater than dopamine greater than noradrenaline greater than serotonin. Similarly, dopaminergic antagonists prevented the photoinactivation of D2 receptors by azidoclebopride with the following order of potency: spiperone greater than (+)-butaclamol greater than haloperidol greater than clebopride greater than (-)-sulpiride greater than (-)-butaclamol

  14. Ventral Tegmental Area Dopamine Cell Activation during Male Rat Sexual Behavior Regulates Neuroplasticity and d-Amphetamine Cross-Sensitization following Sex Abstinence.

    Science.gov (United States)

    Beloate, Lauren N; Omrani, Azar; Adan, Roger A; Webb, Ian C; Coolen, Lique M

    2016-09-21

    Experience with sexual behavior causes cross-sensitization of amphetamine reward, an effect dependent on a period of sexual reward abstinence. We previously showed that ΔFosB in the nucleus accumbens (NAc) is a key mediator of this cross-sensitization, potentially via dopamine receptor activation. However, the role of mesolimbic dopamine for sexual behavior or cross-sensitization between natural and drug reward is unknown. This was tested using inhibitory designer receptors exclusively activated by designer drugs in ventral tegmental area (VTA) dopamine cells. rAAV5/hSvn-DIO-hm4D-mCherry was injected into the VTA of TH::Cre adult male rats. Males received clozapine N-oxide (CNO) or vehicle injections before each of 5 consecutive days of mating or handling. Following an abstinence period of 7 d, males were tested for amphetamine conditioned place preference (CPP). Next, males were injected with CNO or vehicle before mating or handling for analysis of mating-induced cFos, sex experience-induced ΔFosB, and reduction of VTA dopamine soma size. Results showed that CNO did not affect mating behavior. Instead, CNO prevented sexual experience-induced cross-sensitization of amphetamine CPP, ΔFosB in the NAc and medial prefrontal cortex, and decreases in VTA dopamine soma size. Expression of hm4D-mCherry was specific to VTA dopamine cells and CNO blocked excitation and mating-induced cFos expression in VTA dopamine cells. These findings provide direct evidence that VTA dopamine activation is not required for initiation or performance of sexual behavior. Instead, VTA dopamine directly contributes to increased vulnerability for drug use following loss of natural reward by causing neuroplasticity in the mesolimbic pathway during the natural reward experience. Drugs of abuse act on the neural pathways that mediate natural reward learning and memory. Exposure to natural reward behaviors can alter subsequent drug-related reward. Specifically, experience with sexual behavior

  15. The dopamine theory of addiction: 40 years of highs and lows.

    Science.gov (United States)

    Nutt, David J; Lingford-Hughes, Anne; Erritzoe, David; Stokes, Paul R A

    2015-05-01

    For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum. There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.

  16. Structural and Functional Effect of an Oscillating Electric Field on the Dopamine-D3 Receptor: A Molecular Dynamics Simulation Study.

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    Zohreh Fallah

    Full Text Available Dopamine as a neurotransmitter plays a critical role in the functioning of the central nervous system. The structure of D3 receptor as a member of class A G-protein coupled receptors (GPCRs has been reported. We used MD simulation to investigate the effect of an oscillating electric field, with frequencies in the range 0.6-800 GHz applied along the z-direction, on the dopamine-D3R complex. The simulations showed that at some frequencies, the application of an external oscillating electric field along the z-direction has a considerable effect on the dopamine-D3R. However, there is no enough evidence for prediction of changes in specific frequency, implying that there is no order in changes. Computing the correlation coefficient parameter showed that increasing the field frequency can weaken the interaction between dopamine and D3R and may decrease the Arg128{3.50}-Glu324{6.30} distance. Because of high stability of α helices along the z-direction, applying an oscillating electric field in this direction with an amplitude 10-time higher did not have a considerable effect. However, applying the oscillating field at the frequency of 0.6 GHz along other directions, such as X-Y and Y-Z planes, could change the energy between the dopamine and the D3R, and the number of internal hydrogen bonds of the protein. This can be due to the effect of the direction of the electric field vis-à-vis the ligands orientation and the interaction of the oscillating electric field with the dipole moment of the protein.

  17. Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions.

    Science.gov (United States)

    Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V; Field, Bianca; Deutch, Ariel Y; Rayport, Stephen

    2015-12-09

    In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DAT(IREScre) mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome. Dopamine neurons are important for the control of motivated behavior and are involved in the pathophysiology of several major neuropsychiatric disorders. Recent studies have shown that some ventral midbrain dopamine neurons are

  18. Trends in European background air reflect reductions in primary emissions of PCBs and PBDEs.

    Science.gov (United States)

    Schuster, Jasmin K; Gioia, Rosalinda; Breivik, Knut; Steinnes, Eiliv; Scheringer, Martin; Jones, Kevin C

    2010-09-01

    Data are presented for polychlorinated biphenyls (PCBs) and polybrominated diphenyls ethers (PBDEs) in passive air samplers (PAS) collected along a rural/remote latitudinal transect from southern UK to northern Norway during 2004-2008. This study is part of an ongoing campaign, using semipermeable membrane devices (SPMDs) as PAS over two year intervals since 1994. Absolute sequestered amounts of selected PCB congeners have decreased in a first order fashion between 1994-2008, with the average time of 8.4+/-3.2 years for atmospheric concentrations to decline by 50%. PCBs have continued to fractionate with latitude during this period. PBDE concentrations declined by 50% between 2000 and 2008 every 2.2+/-0.4 years. Results are discussed in terms of sources, long-range atmospheric transport, global fractionation, and clearance processes. It is concluded that the spatial and temporal trends in background European air mainly reflect the strength of primary diffusive emissions of these compounds and subsequently their ongoing declines. The direct evidence for this is similar rates of decline at all the sites; similar rates of decline for all congeners; no systematic change in the fractionation pattern since 1994. The latest results indicate a reduction in the rate of decline for PCBs (and hence in primary emissions).

  19. Associations between dioxins/furans and dioxin-like PCBs in estuarine sediment and blue crab

    Science.gov (United States)

    Liebens, J.; Mohrherr, C.J.; Karouna-Renier, N. K.; Snyder, R.A.; Rao, K.R.

    2011-01-01

    The objective of the present study was to evaluate the relationships between the quantity, toxicity, and compositional profile of dioxin/furan compounds (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in estuarine sediment and in the blue crab (Callinectes sapidus). Sediment and blue crab samples were collected in three small urban estuaries that are in relatively close proximity to each other. Results show that differences between PCDD/F and DL-PCB mass concentrations and total toxic equivalents (TEQ) toxicity in sediments of the three estuaries are reflected in those of the blue crab. TEQs are higher in the hepatopancreas of the crabs than in the sediment, but the concentration factor is inversely proportional to the TEQ in the sediments. Congener profiles in the crabs are systematically different from those in the sediments, and the difference is more pronounced for PCDD/Fs than for DL-PCBs, possibly due to differences in metabolization rates. Compared with sediment profiles, more lesser-chlorinated PCDD/Fs that have higher TEFs accumulate in crab hepatopancreas. This selective bioaccumulation of PCDD/Fs results in a TEQ augmentation in crab hepatopancreas compared with sediments. The bioaccumulation in the blue crab is also selective for PCDD/Fs over DL-PCBs. ?? 2011 Springer Science+Business Media B.V.

  20. Biodegradation of PCBs by ligninolytic fungi and characterization of the degradation products

    Czech Academy of Sciences Publication Activity Database

    Čvančarová, Monika; Křesinová, Zdena; Filipová, Alena; Covino, S.; Cajthaml, Tomáš

    2012-01-01

    Roč. 88, č. 11 (2012), s. 1317-1323 ISSN 0045-6535 R&D Projects: GA ČR GA525/09/1058 Institutional support: RVO:61388971 Keywords : Polychlorinated biphenyls * PCBs * Biodegradation Subject RIV: EE - Microbiology, Virology Impact factor: 3.137, year: 2012

  1. Congener Profiles and Source-Wise Phase Partitioning Analysis of PCDDs/Fs and PCBs in Gyeonggi-Do Ambient Air, South Korea

    Directory of Open Access Journals (Sweden)

    Jongwon Heo

    2014-10-01

    Full Text Available The atmospheric concentrations and gas–particle partitioning of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs and polychlorinated biphenyls (PCBs were investigated at two sites (Suwon and Ansan in Gyeonggi-do, a heavily industrialized area of Korea, during the year 2010. The sum level (Σ17 of PCDDs/Fs and dioxin-like PCBs (dl-PCBs in the ambient air at Suwon and Ansan ranged from 0.04 to 0.30 pg-TEQ·m−3 (geometric mean: 0.09 pg-TEQ·m−3 and 0.17 to 0.63 pg-TEQ·m−3 (geometric mean: 0.36 pg-TEQ·m−3, respectively. Moreover, the geometric mean concentrations of Σ180 PCBs at Suwon and Ansan were 233.6 pg·m−3 and 274.2 pg·m−3, respectively, and di-chlorinated biphenyls and tri-chlorinated biphenyls were the predominant homologs. Among the PCB congeners, 3,3'-dichlorobiphenyl (PCB-11 was the dominant species at both sites during all sampling periods, comprising up to 15.1% of Σ180 PCBs at Ansan and 24.6% at Suwon. We evaluated their gas-to-particle equilibriums by conducting regression between the particle–gas partition coefficient Kp (m3·ug−1 and the corresponding subcooled liquid vapor pressure (PL°. The slope (m values for log–log plots of Kp vs. PL° were steeper in industrial areas owing to local source proximity. Moreover, owing to enhanced emissions from combustion-related sources at low temperatures, PCDD/Fs exhibited the largest deviation from the regression line of the particle–gas partition coefficient. Incinerators were found to be the primary emission source of atmospheric PCDDs/Fs, whereas re-evaporation from pre-existing environmental loads (e.g., storage areas or spilled soil and water bodies was the dominant source for PCBs.

  2. Intranasal dopamine reduces in vivo [123I]FP-CIT binding to striatal dopamine transporter: correlation with behavioral changes and evidence for Pavlovian conditioned dopamine response

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    Maria A de Souza Silva

    2016-04-01

    Full Text Available Purpose: Dopamine (DA, which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA, nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor.Methods: Rats were administered intranasal application of 3 mg/kg IN-DA and vehicle (VEH, with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT two hours following administration of the radioligand. Results: 1 After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered dopamine had central action and increased DA levels comparable to that found previously with L-DOPA administration. 2 DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant

  3. Stimulation of accumbal GABAA receptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats.

    Science.gov (United States)

    Aono, Yuri; Kiguchi, Yuri; Watanabe, Yuriko; Waddington, John L; Saigusa, Tadashi

    2017-11-15

    The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABA A receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABA A receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABA A receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were administered intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 25-50min infusions. The delta2-opioid receptor agonist deltorphin II (25.0nmol)- and delta1-opioid receptor agonist DPDPE (5.0nmol)-induced increases in dopamine efflux were inhibited by the delta2-opioid receptor antagonist naltriben (1.5nmol) and the delta1-opioid receptor antagonist BNTX (150.0pmol), respectively. Muscimol (250.0pmol) inhibited deltorphin II (25.0nmol)-induced dopamine efflux. The GABA A receptor antagonist bicuculline (50.0pmol), which failed to affect deltorphin II (25.0nmol)-induced dopamine efflux, counteracted the inhibitory effect of muscimol on deltorphin II-induced dopamine efflux. Neither muscimol (250.0pmol) nor bicuculline (50.0 and 500.0pmol) altered DPDPE (5.0nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA A receptor-mediated inhibition of dopaminergic activity is necessary to produce delta2-opioid receptor-induced increase in accumbal dopamine efflux. This study indicates that activation of delta2- but not delta1-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA A receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Concentrations of dioxins and dioxin-like PCBs in feed materials in the Netherlands, 2001-11.

    Science.gov (United States)

    Adamse, Paulien; Van der Fels-Klerx, H J Ine; Schoss, Stefanie; de Jong, Jacob; Hoogenboom, Ron L A P

    2015-01-01

    This study aimed to obtain insights into contamination of feed materials used in the Netherlands with dioxins (polychlorinated dibenzo-p-dioxins and dibenzofurans) and dioxin-like polychlorinated biphenyls (PCBs). Monitoring results from the period 2001-11, covering in total 4938 samples, were statistically analysed and evaluated against the statutory limits set at the beginning or during this period. The percentage of samples exceeding maximum levels set within the European Union for either dioxins or the sum of dioxins and dioxin-like PCBs were below 1% for most feed categories, except for fish meal (4.1%), clay minerals (binders and anti-caking agents) (3.4%), and vegetable oils and byproducts (1.7%). For most feed categories, non-compliance with the action threshold (roughly 33% lower than maximum levels) for either dioxins or dioxin-like PCBs was up to three times higher than non-compliance with the respective maximum levels. Exceedance of action thresholds was just above 1% for animal fat, pre-mixtures and feed materials of plant origin excluding vegetable oils. For the categories fish meal, clay minerals, and vegetable oils and byproducts, the action thresholds were exceeded by 5.0%, 9.8% and 3.0% of the samples, respectively. In general, the percentages of samples that exceeded the action thresholds and maximum levels were lower than those reported for the European Union by the European Food Safety Authority (EFSA). In most of the feed materials, there seems to be a decreasing trend in concentrations of dioxins or dioxin-like PCBs over the years. However, a lowering of the limits of quantification during this period and the low concentrations in most samples precludes drawing strong conclusions.

  5. The role of dopamine receptors in the neurotoxicity of methamphetamine.

    Science.gov (United States)

    Ares-Santos, S; Granado, N; Moratalla, R

    2013-05-01

    Methamphetamine is a synthetic drug consumed by millions of users despite its neurotoxic effects in the brain, leading to loss of dopaminergic fibres and cell bodies. Moreover, clinical reports suggest that methamphetamine abusers are predisposed to Parkinson's disease. Therefore, it is important to elucidate the mechanisms involved in methamphetamine-induced neurotoxicity. Dopamine receptors may be a plausible target to prevent this neurotoxicity. Genetic inactivation of dopamine D1 or D2 receptors protects against the loss of dopaminergic fibres in the striatum and loss of dopaminergic neurons in the substantia nigra. Protection by D1 receptor inactivation is due to blockade of hypothermia, reduced dopamine content and turnover and increased stored vesicular dopamine in D1R(-/-) mice. However, the neuroprotective impact of D2 receptor inactivation is partially dependent on an effect on body temperature, as well as on the blockade of dopamine reuptake by decreased dopamine transporter activity, which results in reduced intracytosolic dopamine levels in D2R(-/-) mice. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  6. Functional characterization of dopamine transporter in vivo using Drosophila melanogaster behavioral analysis.

    Directory of Open Access Journals (Sweden)

    Taro eUeno

    2014-09-01

    Full Text Available Dopamine mediates diverse functions such as motivation, reward, attention, learning/memory and sleep/arousal. Recent studies using model organisms including the fruit fly, have elucidated various physiological functions of dopamine, and identified specific neural circuits for these functions. Flies with mutations in the Drosophila dopamine transporter (dDAT gene show enhanced dopamine signaling, and short sleep and memory impairment phenotypes. However, understanding the mechanism by which dopamine signaling causes these phenotypes requires an understanding of the dynamics of dopamine release. Here we report the effects of dDAT expression on behavioral traits. We show that dDAT expression in a subset of dopaminergic neurons is sufficient for normal sleep. dDAT expression in other cell types such as Kenyon cells and glial cells can also rescue the short sleep phenotype of dDAT mutants. dDAT mutants also show a down-regulation of the D1-like dopamine receptor dDA1, and this phenotype is rescued when dDAT is expressed in the same cell types in which it rescues sleep. On the other hand, dDAT overexpression in mushroom bodies, which are the target of memory forming dopamine neurons, abolishes olfactory aversive memory. Our data demonstrate that expression of extrasynaptic dopamine transporters can rescue some aspects of dopamine signaling in dopamine transporter mutants. These results provide novel insights into regulatory systems that modulate dopamine signaling.

  7. Organochlorine pesticides residues and PCBs in benthic organisms of the inner shelf of the São Sebastião Channel, São Paulo, Brazil

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    Rosângela Gorni

    2004-06-01

    Full Text Available Thirty seven benthic samples of the inner shelf area of São Sebastião, Brazil, were collected between April 1994 and August 1998 and analysed for seventeen chlorinated pesticide residues and PCBs congeners. Pesticide residues and PCBs congeners levels were low (ng/g and predominantly found in the crustacean samples. DDE was the most frequently residue with a maximum of 9,7 ng/g followed by HCHs with maximum of 17,1ng/g. As for the PCBs, the heavier congeners predominate: CB 138,153,170, 180 and 183. Maximum total PCBs was 17,4 ug/g in a crab sample. Higher levels of PCBs are related to feeding habits and local inputs of raw sewage or land runoff. Although EPA and FDA (U.S.A below the guidelines for human consumption propose these levels, they do show that even in marine areas without intense agricultural or industrial activities these compounds are present at detectable levels.Trinta e sete amostras de bentos da área interna do Canal de São Sebastião, Brasil, foram coletadas entre Abril de 1994 e Agosto de 1998 e analisadas quanto aos níveis de resíduos de 17 pesticidas organoclorados os congêneres dos PCBs. Os níveis de resíduos de organoclorados e PCBs foram baixos( ng/g e encontrados com maior freqüência nas amostras de crustáceos. DDE foi o resíduo de pesticida encontrado com mais freqüência apresentado um máximo de 9,7 ng/g seguido dos isômeros de HCHs com um máximo de 17,1 ng/g. No caso dos PCBs os congêneres mais pesados foram os predominantes: CB 138, 153, 170, 180 e 183. O valor máximo de PCBs totais foi de 17,4 ug/g numa amostra de crustáceo. Níveis maiores de PCBs estão associados aos hábitos alimentares e introduções pontuais de esgotos e água de drenagem urbana. Apesar dos níveis observados estarem abaixo dos recomendados para consumo humano pela EPA e da FDA( U.S.A ,eles demonstram que mesmo em área marinhas costeiras sem agricultura intensiva ou atividades industriais de porte , estes compostos org

  8. Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

    Science.gov (United States)

    Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

    2018-04-15

    Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

  9. Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

    Science.gov (United States)

    Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

    2018-05-01

    l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D 2 -dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T 0 AM and T 1 AM in vitro . Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T 1 AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. © 2018 The authors.

  10. PCBs and PCDD/Fs distribution in tissues and organs of marine animals in Russian Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Amirova, Z.; Kruglov, E.; Loshkina, E.; Khalilov, R. [Environmental Research and Protection Centre, Ufa (Russian Federation); Melnikov, S.; Vlasov, S. [Regional Centre Monitoring of the Arctic, St. Petersburg (Russian Federation)

    2004-09-15

    Studies of persistent organic pollutants (POPs) in the Russian Arctic were conducted recently by a Arctic Monitoring and Assessment Program (AMAP) project. This project developed new data on the POPs pollution levels in the environment and biosphere, including PCBs and PCDD/Fs, in arctic regions of Russia. Transboundary transport and biomagnification within food chains in arctic regions result in POPs accumulation in tissues of fish and marine animals. The aim of this study was to determine the concentration of indicator PCBs, co-planar PCBs and PCDD/Fs in different tissues and organs of seals, walruses and whales caught near the seashore of Chukotski Peninsula (settlement of Lavrenty), Russia, to determine the background level of arctic biota pollution and to study distribution of toxicants in organisms of marine animals. Sampling was made in the course of the 1{sup st} and the 2{sup nd} stages of the 4{sup th} phase of Raipon/AMAP/GEF project ''Persistent Toxic Substances (PTS), Food Security and Indigenous Peoples of the Russian North'' in 2002 by researchers of the Regional Center for Monitoring of the Arctic (RCMA), St. Petersburg, Russia.

  11. Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout.

    Directory of Open Access Journals (Sweden)

    Frank Scott Hall

    Full Text Available Knockout (KO mice that lack the dopamine transporter (SL6A3; DAT display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD and that these drugs may act upon serotonin (5-HT systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics.

  12. Dopamine and serotonin levels following prenatal viral infection in mouse--implications for psychiatric disorders such as schizophrenia and autism.

    Science.gov (United States)

    Winter, Christine; Reutiman, Teri J; Folsom, Timothy D; Sohr, Reinhard; Wolf, Rainer J; Juckel, Georg; Fatemi, S Hossein

    2008-10-01

    Prenatal viral infection has been associated with neurodevelopmental disorders such as schizophrenia and autism. It has previously been demonstrated that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) and middle-late second trimester (E18) administration of influenza virus. Neurochemical analysis following infection on E18 using this model has revealed significantly altered levels of serotonin, 5-hydroxyindoleacetic acid, and taurine, but not dopamine. In order to monitor these different patterns of monoamine expression in exposed offspring in more detail and to see if there are changes in the dopamine system at another time point, pregnant C57BL6J mice were infected with a sublethal dose of human influenza virus or sham-infected using vehicle solution on E16. Male offspring of the infected mice were collected at P0, P14, and P56, their brains removed and cerebellum dissected and flash frozen. Dopamine and serotonin levels were then measured using HPLC-ED technique. When compared to controls, there was a significant decrease in serotonin levels in the cerebella of offspring of virally exposed mice at P14. No differences in levels of dopamine were observed in exposed and control mice, although there was a significant decrease in dopamine at P14 and P56 when compared to P0. The present study shows that the serotonergic system is disrupted following prenatal viral infection, potentially modelling disruptions that occur in patients with schizophrenia and autism.

  13. Peripartum Cardiomyopathy Treatment with Dopamine Agonist and Subsequent Pregnancy with a Satisfactory Outcome.

    Science.gov (United States)

    Melo, Maria Adélia Medeiros E; Carvalho, Jordão Sousa; Feitosa, Francisco Edson de Lucena; Araujo Júnior, Edward; Peixoto, Alberto Borges; Costa Carvalho, Francisco Herlânio; Carvalho, Regina Coeli Marques

    2016-06-01

    Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases. Thieme Publicações Ltda Rio de Janeiro, Brazil.

  14. Antibodies to dopamine: radioimmunological study of specificity in relation to immunocytochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Geffard, M.; Kah, O.; Onteniente, B.; Seguela, P.; Le Moal, M.; Delaage, M.

    1984-06-01

    Two classes of anti-3,4- dihydroxyphenylethylamine (dopamine) antibodies were raised in rabbits using dopamine conjugated to albumin either via formaldehyde or via glutaraldehyde. Each was usable for immunohistochemical detection of dopamine neurons provided that the tissue was fixed by the homologous cross-linking agent. However, anti-dopamine-glutaraldehyde antibodies turned out to be of more general use because of the better fixative properties of glutaraldehyde which fixed dopamine in rat and in teleost, whereas formaldehyde only worked in lower vertebrates (such as goldfish) and not in rat brain. The specificity of anti-dopamine-glutaraldehyde antibodies was firmly established by competition experiments in equilibrium dialysis, using an immunoreactive tritiated derivative synthesized by coupling dopamine to N-alpha-acetyl-L-lysine N-methylamide via glutaraldehyde. Specificity studies in vitro and immunohistological results demonstrating the specific staining of dopaminergic neurons were found to correlate well.

  15. Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in sediments from the Gulf of Batabanó, Cuba.

    Science.gov (United States)

    Alonso-Hernandez, C M; Mesa-Albernas, M; Tolosa, I

    2014-01-01

    The spatial distribution of various organochlorinated compounds, e.g. PCBs, DDTs, HCB and HCHs, were investigated in sediments of the Gulf of Batabanó, Cuba. Among the target organochlorine compounds measured, ΣDDT isomers were the predominant contaminant with concentrations ranging from 0.019 to 1.27 ng g(-1)dry wt. Lindane was present at very low concentrations in the range n.d. to 0.05 ng g(-1), while PCBs and other organochlorine pesticide residues, such as HCB, Heptaclor, Aldrin and Mirex were lower than detection limits (∼0.010 ng g(-1)). According to established sediment quality guidelines, the OCPs concentrations encountered in the surface sediments are probably not having an adverse effect on sediment dwelling organisms. Compared to concentrations reported in coastal environments from other parts of the world, PCBs and OCs concentrations in surface sediments of Batabanó Gulf were low and similar to the reported for remote and pristine environments. These results contribute to the sparse regional database for organochlorinated compounds in the Caribbean marine environment. Copyright © 2013. Published by Elsevier Ltd.

  16. Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor.

    Directory of Open Access Journals (Sweden)

    Daniela Betiana Radl

    Full Text Available Dopamine, through D2 receptor (D2R, is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L and short (D2S, are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850. SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

  17. Effects of cysteamine on dopamine-mediated behaviors: evidence for dopamine-somatostatin interactions in the striatum

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Iverson, M.T.; Radke, J.M.; Vincent, S.R.

    1986-06-01

    The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine-induced stereotypy was attenuated and striatal somatostatin levels were reduced by half. Systemic cysteamine also decreased the motor stimulant effects of amphetamine, without influencing the rewarding properties as determined by the conditioned place preference procedure. Direct injections of cysteamine into the nucleus accumbens also decreased the locomotor response to amphetamine, and produced a local reduction in somatostatin levels in the accumbens. Cysteamine did not appear to alter monoamine turnover in the striatum after either systemic or intra-accumbens injections. These results suggest that somatostatin in the nucleus accumbens and caudate-putamen modulates the motor, but not the reinforcing properties of dopaminergic drugs, possibly via an action postsynaptic to dopamine-releasing terminals. Furthermore, it is evident from these results that cysteamine is an important tool with which to study the central actions of somatostatin.

  18. Trophic Magnification of PCBs and Its Relationship to the Octanol−Water Partition Coefficient

    Science.gov (United States)

    We investigated polychlorinated biphenyl (PCB) bioaccumulation relative to octanol-water partition coefficient (KOW) and organism trophic position (TP) at the Lake Hartwell Superfund (South Carolina, USA). We measured PCBs (127 congeners) and stable isotopes (δ15...

  19. Compilations of measured and calculated physicochemical property values for PCBs, PBDEs, PCDDs and PAHs

    Data.gov (United States)

    U.S. Environmental Protection Agency — The dataset consists of compilations of measured and calculated physicochemical property values for PCBs, PBDEs, PCDDs and PAHs. The properties included in this...

  20. Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

    Science.gov (United States)

    Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

    2016-05-01

    Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety

  1. Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

    Science.gov (United States)

    Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

    2016-05-04

    The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] μmol/kg) greater than dopamine (190 [181-203] μmol/kg) (Pbupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Dopamine en overmatig alcoholgebruik: genen in interactie met hun omgeving [Dopamine and excessive alcohol consumption: how genes interact with their environment

    OpenAIRE

    Schellekens, A.F.A.; Scholte, R.H.J.; Engels, R.C.M.E.; Verkes, R.J.

    2013-01-01

    background Hereditary factors account for approximately 50% of the risk of developing alcohol dependence. Genes that affect the dopamine function in the brain have been extensively studied as candidate genes. aim To present the results of recent Dutch studies on the interaction between genes and their environment in relation to dopamine function and excessive alcohol use. method Two large scale research projects were recently carried out in order to study the relation between dopamine genes a...

  3. The dopamine hypothesis of drug addiction and its potential therapeutic value.

    Directory of Open Access Journals (Sweden)

    Marco eDiana

    2011-11-01

    Full Text Available Dopamine (DA transmission is deeply affected by drugs of abuse, and alterations in DA function are involved in various phases of drug addiction and potentially exploitable therapeutically. In particular, basic studies have documented a reduction in the electrophysiological activity of DA neurons in alcohol, opiate, cannabinoid and other drug-dependent rats. Further, DA release in the Nacc is decreased in virtually all drug-dependent rodents. In parallel, these studies are supported by increments in intracranial self stimulation (ICSS thresholds during withdrawal from alcohol, nicotine, opiates, and other drugs of abuse, thereby suggesting a hypofunction of the neural substrate of ICSS. Accordingly, morphological evaluations fed into realistic computational analysis of the Medium Spiny Neuron (MSN of the Nucleus accumbens (Nacc, post-synaptic counterpart of DA terminals, show profound changes in structure and function of the entire mesolimbic system. In line with these findings, human imaging studies have shown a reduction of dopamine receptors accompanied by a lesser release of endogenous DA in the ventral striatum of cocaine, heroin and alcohol-dependent subjects, thereby offering visual proof of the ‘dopamine-impoverished’ addicted human brain.The reduction in physiological activity of the DA system leads to the idea that an increment in its activity, to restore pre-drug levels, may yield significant clinical improvements (reduction of craving, relapse and drug-seeking/taking. In theory, it may be achieved pharmacologically and/or with novel interventions such as Transcranial Magnetic Stimulation (TMS. Its anatomo-physiological rationale as a possible therapeutic aid in alcoholics and other addicts will be described and proposed as a theoretical framework to be subjected to experimental testing in human addicts.

  4. Dioxins and PCBs in ostrich meat and eggs: levels and implications.

    Science.gov (United States)

    Piskorska-Pliszczynska, Jadwiga; Strucinski, Pawel; Mikolajczyk, Szczepan; Pajurek, Marek; Maszewski, Sebastian; Pietron, Wojciech

    2017-12-01

    Although consumption of eggs is an essential part of our diet, limited information is available for table eggs other than those laid by hens. The aim of our study was to determine concentrations of polychlorinated dibenzofurans (PCDD/Fs), dioxin-like (DL-) and non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) in ostrich eggs and meat available on the Polish market, in order to obtain baseline information on the current status of these pollutants in comparison to poultry products. Obtained data were compared with the binding EU limits set for chicken eggs and meat. The levels of individual PCDD/Fs and PCBs congeners varied considerably. The percentage share of total WHO toxic equivalency factor (WHO-TEQ) content indicates the dominant role of PCDD/Fs. High concentrations of PCDD/F and DL-PCBs, in the range of 0.85-74.48 pg WHO-TEQ g -1 fat, were found in ostrich eggs; this exceeds the maximum level permitted for chicken eggs by a factor of up to 15. Eight of the 11 egg samples exceeded the action level for hen eggs. Although the ostrich meat concentrations of PCDD/Fs do not exceed the limit established for poultry muscle (1.75 pg g -1 fat), average contents of PCDD/Fs exceeded almost four times the levels in chicken and turkey muscle. Human exposure was evaluated and the resulting risk was characterised. Taking into account the low average consumption of ostrich eggs, the resulting exposure to dioxins for the general population can be considered as negligibly low. However, the individuals who frequently consume such eggs may be at risk of elevated exposure. Although ostrich products are not consumed frequently, such data are nevertheless useful for food safety purposes.

  5. Dopamine and extinction: a convergence of theory with fear and reward circuitry.

    Science.gov (United States)

    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2014-02-01

    Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. The role of dopamine in human addiction: from reward to motivated attention.

    Science.gov (United States)

    Franken, Ingmar H A; Booij, Jan; van den Brink, Wim

    2005-12-05

    There is general consensus among preclinical researchers that dopamine plays an important role in the development and persistence of addiction. However, the precise role of dopamine in addictive behaviors is far from clear and only a few clinical studies on the role of dopamine in human addiction have been conducted so far. The present paper reviews studies addressing the role of dopamine in humans. There is substantial and consistent evidence that dopamine is involved in the experience of drug reward in humans. Dopamine may also be involved in motivational processes such as drug craving. However, given the inconsistent findings of studies using dopamine receptor (ant)agonists, the role of dopamine in the experience of craving is far from resolved. Recent theories claiming that dopamine signals salience and makes the brain paying attention to biological relevant stimuli may provide an interesting framework for explaining addictive behaviors. There is accumulating evidence that patients with drug and alcohol addiction have an aberrant focus on drug-related stimuli. Although there is some preliminary support for the role of dopamine in these attention processes, more studies have to be carried out in order to test the validity of these theories in human subjects.

  7. Task 3 Report - PCBs in the Environment Near the Oak Ridge Reservation - A Reconstruction of Historical Doses and Health Risks

    Energy Technology Data Exchange (ETDEWEB)

    Price, Paul S; Widner, Thomas; Bonnevie, Nancy; Schmidt, Charlie; McCrodden-Hamblen, Jane; Vantaggio, Joanne; Gwinn, Patrick

    1999-07-01

    This report presents the results of an in-depth assessment of historical releases of polychlorinated biphenyls (PCBs) from the Oak Ridge Reservation (ORR) and risks of adverse health effects in local populations. The study was conducted by ChemRisk, a service of McLaren/Hart, Inc., for the Tennessee Department of Health. The project team (1) investigated releases of PCBs from the government sites, (2) evaluated PCB levels in environmental media in the area, (3) described releases of PCBs from other sources in the area, and (4) evaluated potential human exposures and health impacts associated with the historical presence of these contaminants in the environment. Beginning in the 1940s, PCBs were used extensively on the ORR and throughout the U.S. as a fire retardant in electrical components. PCBs were also used as cutting fluids for lubrication and cooling during metal working operations. Using information specific to the ORR, the project team estimated health risks for five off-site populations: (1) farm families that raised beef, dairy cattle, and vegetables on the flood plain of East Fork Poplar Creek (EFPC); (2) individuals who may have purchased beef and milk from cattle raised in the EFPC flood plain; (3) commercial and recreational fish consumers; (4) individuals that may have consumed turtles; and (5) users of surface water for recreation. Noteworthy features of the study include a two-dimensional analysis of uncertainty and variability in the non-cancer risk estimates and an assessment of the uncertainty in PCB toxicology thresholds. Conservative estimates of cancer risks from the ORR releases of PCBs to consumers of fish from Watts Bar Reservoir and the Clinch River range from less than 1 in a 1,000,000 to 2 in 10,000. Three or less excess cases of cancer would be expected to occur among individuals who consumed fish from these local waters since the 1940's. Persons who consumed large amounts of fish from the Clinch R. and Watts Bar were also at risk

  8. Striatal dopamine D2 receptor binding and dopamine release during cue-elicited craving in recently abstinent opiate-dependent males

    NARCIS (Netherlands)

    Zijlstra, Fleur; Booij, Jan; van den Brink, Wim; Franken, Ingmar H. A.

    2008-01-01

    Opiate addiction is a chronic disorder characterized by relapse behaviour, often preceded by craving and anhedonia. Chronic craving and anhedonia have been associated with low availability of dopamine D2 receptors (D2Rs) and cue-elicited craving has been linked with endogenous dopamine release. We

  9. Dopamine does double duty in motivating cognitive effort

    Science.gov (United States)

    Westbrook, Andrew; Braver, Todd S.

    2015-01-01

    Cognitive control is subjectively costly, suggesting that engagement is modulated in relationship to incentive state. Dopamine appears to play key roles. In particular, dopamine may mediate cognitive effort by two broad classes of functions: 1) modulating the functional parameters of working memory circuits subserving effortful cognition, and 2) mediating value-learning and decision-making about effortful cognitive action. Here we tie together these two lines of research, proposing how dopamine serves “double duty”, translating incentive information into cognitive motivation. PMID:26889810

  10. Prefrontocortical dopamine loss in rats delays long-term extinction of contextual conditioned fear, and reduces social interaction without affecting short-term social interaction memory.

    Science.gov (United States)

    Fernandez Espejo, Emilio

    2003-03-01

    Prefrontal dopamine loss delays extinction of cued fear conditioning responses, but its role in contextual fear conditioning has not been explored. Medial prefrontal lesions also enhance social interaction in rats, but the role of prefrontal dopamine loss on social interaction memory is not known. Besides, a role for subcortical accumbal dopamine on mnesic changes after prefrontal dopamine manipulation has been proposed but not explored. The objective was to study the involvement of dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) and nucleus accumbens in two mnesic tasks: contextual fear conditioning and social interaction memory. For contextual fear conditioning, short- and long-term freezing responses after an electric shock were studied, as well as extinction retention. Regarding social interaction memory, the recognition of a juvenile, a very sensitive short-term memory test, was used. Dopamine loss was carried out by injection of 6-hydroxydopamine, and postmortem catecholamine levels were analyzed by high-performance liquid chromatography. Prefrontocortical dopamine loss (>76%) led to a reactive enhancement of accumbal dopamine content (ploss. In lesioned rats, long-term extinction of contextual fear conditioning was significantly delayed and extinction retention was impaired without changes in acquisition and short-term contextual fear conditioning and, on the other hand, acquisition and short-term social interaction memory were not affected, although time spent on social interaction was significantly reduced. Added dopamine loss in the nucleus accumbens (>76%) did not alter these behavioral changes. In summary, the results of the present study indicate that the dopaminergic network in the mPFC (but not in the nucleus accumbens) coordinates the normal long-term extinction of contextual fear conditioning responses without affecting their acquisition, and it is involved in time spent on social interaction, but not acquisition and short

  11. Alteration in adenylate cyclase response to aminergic stimulation following neonatal x-irradiation

    International Nuclear Information System (INIS)

    Chronister, R.B.; Palmer, G.C.; Gerbrandt, L.

    1980-01-01

    X-irradiation of the rat neonatal hippocampus produces severe alterations in the architectonic features of the mature hippocampus. The most prominent alteration is a marked depletion of the granule cells of the dentate gyrus, with a subsequent realignment of CA 4 cells. The present data also show that norepinephrine (NE), dopamine and histamine stimulation of adenylate cyclase activity is severely attenuated in the hippocampi of irradiated animals. This failure suggests that the NE fibers of irradiated subjects, although normal in content of NE, are not functional in some of their NE-effector actions

  12. Reward-based hypertension control by a synthetic brain-dopamine interface.

    Science.gov (United States)

    Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

    2013-11-05

    Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

  13. Zero-Valent Metallic Treatment System and Its Application for Removal and Remediation of Polychlorinated Biphenyls (Pcbs)

    Science.gov (United States)

    Quinn, Jacqueline W. (Inventor); Clausen, Christian A. (Inventor); Geiger, Cherie L. (Inventor); Brooks, Kathleen B. (Inventor)

    2012-01-01

    PCBs are removed from contaminated media using a treatment system including zero-valent metal particles and an organic hydrogen donating solvent. The treatment system may include a weak acid in order to eliminate the need for a coating of catalytic noble metal on the zero-valent metal particles. If catalyzed zero-valent metal particles are used, the treatment system may include an organic hydrogen donating solvent that is a non-water solvent. The treatment system may be provided as a "paste-like" system that is preferably applied to natural media and ex-situ structures to eliminate PCBs.

  14. Dioxins and dl-PCBs in gull eggs from Spanish Natural Parks (2010-2013).

    Science.gov (United States)

    Morales, Laura; Gene'rosa Martrat, Ma; Parera, Jordi; Bertolero, Albert; Ábalos, Manuela; Santos, Francisco Javier; Lacorte, Silvia; Abad, Esteban

    2016-04-15

    The aim of this study was to evaluate the presence and distribution of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and biphenyls (PCBs), concretely those so-called as dioxin-like PCBs, in yellow-legged gull eggs (Larus michahellis) collected from five Natural Parks (some of them National Parks) in Spain during the period 2010-2013. PCDD/Fs and dl-PCBs were detected in all the samples. Due to the proximity to important urban and industrial areas higher concentrations were determined in colonies located in the Northern Mediterranean coast than those found in the Southern Mediterranean or Atlantic colonies where a softer anthropogenic impact occurs. Mean ∑PCDD/F concentrations ranged from 49 to 223pg/g lipid weight (lw) and ∑dl-PCB concentrations varied from 146 to 911ng/g lw. In the Natural Park of the Ebro Delta (Northern Mediterranean coast) two gull species share habitat: yellow-legged and Audouin gull (Larus audouinii). Eggs from both species were collected and PCDD/F and dl-PCB levels compared. The species that feeds exclusively on pelagic fish (L. audouinii) had significantly higher PCDD/F and dl-PCB levels than the scavenger L. michahellis, pointing out the diet-dependent differences in the accumulation of persistent organic pollutants between similar cohabitant breeding species. Finally, mean TEQ values were in general below those considered as critical for toxicological effects in birds. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain—striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [11C]raclopride to measure...... dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  16. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C......]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  17. Development and Application of Immunoaffinity Chromatography for Coplanar PCBs in Soil and Sediment

    Science.gov (United States)

    An immunoaffinity chromatography (IAC) column was developed as a simple cleanup procedure for preparing environmental samples for analysis of polychlorinated biphenyls (PCBs). Soil and sediment samples were prepared using pressurized liquid extraction (PLE), followed by the IAC c...

  18. The effects of surgical and chemical lesions on striatal [3H]threo-(+-)-methylphenidate binding: correlation with [3H]dopamine uptake

    International Nuclear Information System (INIS)

    Janowsky, A.; Berger, P.; Long, R.; Paul, S.M.; Schweri, M.M.; Skolnick, P.

    1985-01-01

    The specific binding of [ 3 H]threo-(+-)-methylphenidate to membranes prepared from rat striatum was significantly reduced following either surgical lesions of the medial forebrain bundle or intracerebroventricular administration of 6-hydroxydopamine. The decrease in the density of [ 3 H]threo-(+-)-methylphenidate binding sites in striatum following chemical or surgical denervation was highly correlated with the decrease in [ 3 H]dopamine uptake. In contrast, intracerebroventricular administration of 5,7-dihydroxytryptamine, AF64A, or chronic parenteral administration of reserpine did not alter either the number or apparent affinity of [ 3 H]threo-(+-)-methylphenidate binding sites. These data suggest that the specific binding sites for [ 3 H]threo-(+-)-methylphenidate in striatum are localized to dopaminergic nerve terminals, and may be associated with the dopamine transport complex. (orig.)

  19. Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia.

    Science.gov (United States)

    Farré, Daniel; Muñoz, Ana; Moreno, Estefanía; Reyes-Resina, Irene; Canet-Pons, Júlia; Dopeso-Reyes, Iria G; Rico, Alberto J; Lluís, Carme; Mallol, Josefa; Navarro, Gemma; Canela, Enric I; Cortés, Antonio; Labandeira-García, José L; Casadó, Vicent; Lanciego, José L; Franco, Rafael

    2015-12-01

    Radioligand binding assays to rat striatal dopamine D1 receptors showed that brain lateralization of the dopaminergic system were not due to changes in expression but in agonist affinity. D1 receptor-mediated striatal imbalance resulted from a significantly higher agonist affinity in the left striatum. D1 receptors heteromerize with dopamine D3 receptors, which are considered therapeutic targets for dyskinesia in parkinsonian patients. Expression of both D3 and D1-D3 receptor heteromers were increased in samples from 6-hydroxy-dopamine-hemilesioned rats rendered dyskinetic by treatment with 3, 4-dihydroxyphenyl-L-alanine (L-DOPA). Similar findings were obtained using striatal samples from primates. Radioligand binding studies in the presence of a D3 agonist led in dyskinetic, but not in lesioned or L-DOPA-treated rats, to a higher dopamine sensitivity. Upon D3-receptor activation, the affinity of agonists for binding to the right striatal D1 receptor increased. Excess dopamine coming from L-DOPA medication likely activates D3 receptors thus making right and left striatal D1 receptors equally responsive to dopamine. These results show that dyskinesia occurs concurrently with a right/left striatal balance in D1 receptor-mediated neurotransmission.

  20. Demonstration of specific dopamine receptors on human pituitary adenomas

    Energy Technology Data Exchange (ETDEWEB)

    Koga, Masafumi; Nakao, Haruyoshi; Arao, Masayo; Sato, Bunzo; Noma, Keizo; Morimoto, Yasuhiko; Kishimoto, Susumu; Mori, Shintaro; Uozumi, Toru

    1987-01-01

    Dopamine receptors on human pituitary adenoma membranes were characterized using (/sup 3/H)spiperone as the radioligand. The specific (/sup 3/H)spiperone binding sites on prolactin (PRL)-secreting adenoma membranes were recognized as a dopamine receptor, based upon the data showing high affinity binding, saturability, specificity, temperature dependence, and reversibility. All of 14 PRL-secreting adenomas had high affinity dopamine receptors, with a dissociation constant (Kd) of 0.85 +- 0.11 nmol/l (mean+-SEM) and a maximal binding capacity (Bmax) of 428 +- 48.6 fmol/mg protein. Among 14 growth hormone (GH)-secreting adenomas examined, 8 (57%) had dopamine receptors with a Kd of 1.90 +- 0.47 nmol/l and a Bmax of 131 +- 36.9 fmol/mg protein. Furthermore, 15 of 24 (58%) nonsecreting pituitary adenomas also had dopamine receptors with a Kd of 1.86 +- 0.37 nmol/l and a Bmax of 162 +- 26.0 fmol/mg protein. These results indicate that some GH-secreting adenomas as well as some nonsecreting pituitary adenomas contain dopamine receptors. But their affinity and number of binding sites are significantly lower (P<0.05) and fewer (P<0.001) respectively, than those in PRL-secreting adenomas.

  1. Dopamine Signaling Regulates Fat Content through β-Oxidation in Caenorhabditis elegans

    Science.gov (United States)

    Barros, Alexandre Guimarães de Almeida; Bridi, Jessika Cristina; de Souza, Bruno Rezende; de Castro Júnior, Célio; de Lima Torres, Karen Cecília; Malard, Leandro; Jorio, Ado; de Miranda, Débora Marques; Ashrafi, Kaveh; Romano-Silva, Marco Aurélio

    2014-01-01

    The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots. PMID:24465759

  2. Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene.

    Science.gov (United States)

    Vengeliene, Valentina; Bespalov, Anton; Roßmanith, Martin; Horschitz, Sandra; Berger, Stefan; Relo, Ana L; Noori, Hamid R; Schneider, Peggy; Enkel, Thomas; Bartsch, Dusan; Schneider, Miriam; Behl, Berthold; Hansson, Anita C; Schloss, Patrick; Spanagel, Rainer

    2017-04-01

    The research domain criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here, we used a new genetic rat model with a loss-of-function point mutation in the dopamine transporter (DAT) gene ( Slc6a3 _N157K) to systematically study the RDoC matrix. First, we examined the impact of the Slc6a3 _N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains: negative and positive valence systems, cognitive, social and arousal/regulatory systems. The use of RDoC may be particularly helpful for drug development. We studied the effects of a novel pharmacological approach metabotropic glutamate receptor mGluR2/3 antagonism, in DAT mutants in a comparative way with standard medications. Loss of DAT functionality in mutant rats not only elevated subcortical extracellular dopamine concentration but also altered the balance of monoaminergic transmission. DAT mutant rats showed deficits in all five RDoC domains. Thus, mutant rats failed to show conditioned fear responses, were anhedonic, were unable to learn stimulus-reward associations, showed impaired cognition and social behavior, and were hyperactive. Hyperactivity in mutant rats was reduced by amphetamine and atomoxetine, which are well-established medications to reduce hyperactivity in humans. The mGluR2/3 antagonist LY341495 also normalized hyperactivity in DAT mutant rats without affecting extracellular dopamine levels. We systematically characterized an altered dopamine system within the context of the RDoC matrix and studied mGluR2/3 antagonism as a new pharmacological strategy to treat mental disorders with underlying subcortical dopaminergic hyperactivity. © 2017. Published by The Company of Biologists Ltd.

  3. Quantum chemical study of TiO2/dopamine-DNA triads

    International Nuclear Information System (INIS)

    Vega-Arroyo, Manuel; LeBreton, Pierre R.; Zapol, Peter; Curtiss, Larry A.; Rajh, Tijana

    2007-01-01

    Photoinduced charge separation in triads of DNA covalently linked to an anatase nanoparticle via a dopamine bridge was studied by ab initio calculations of the oxidation potentials of carboxyl-DNA trimers and the TiO 2 /dopamine complex. Conjugation of dopamine to the TiO 2 surface results in a lower oxidation potential of the complex relative to the surface and in localization of photogenerated holes on dopamine, while photogenerated electrons are excited into the conduction band of TiO 2 . Linking dopamine to the DNA trimers at the 5' end of the oligonucleotide may lead to further hole migration to the DNA. Calculations show that for several different sequences hole migration is favorable in double stranded DNA and unfavorable in single-stranded DNA. This extended charge separation was shown to follow from the redox properties of DNA sequence rather than from the modification of DNA's electron donating properties by the dopamine linker, which explains experimental observations

  4. Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT.

    Science.gov (United States)

    Aguilar, Jenny I; Dunn, Matthew; Mingote, Susana; Karam, Caline S; Farino, Zachary J; Sonders, Mark S; Choi, Se Joon; Grygoruk, Anna; Zhang, Yuchao; Cela, Carolina; Choi, Ben Jiwon; Flores, Jorge; Freyberg, Robin J; McCabe, Brian D; Mosharov, Eugene V; Krantz, David E; Javitch, Jonathan A; Sulzer, David; Sames, Dalibor; Rayport, Stephen; Freyberg, Zachary

    2017-08-30

    The ability of presynaptic dopamine terminals to tune neurotransmitter release to meet the demands of neuronal activity is critical to neurotransmission. Although vesicle content has been assumed to be static, in vitro data increasingly suggest that cell activity modulates vesicle content. Here, we use a coordinated genetic, pharmacological, and imaging approach in Drosophila to study the presynaptic machinery responsible for these vesicular processes in vivo. We show that cell depolarization increases synaptic vesicle dopamine content prior to release via vesicular hyperacidification. This depolarization-induced hyperacidification is mediated by the vesicular glutamate transporter (VGLUT). Remarkably, both depolarization-induced dopamine vesicle hyperacidification and its dependence on VGLUT2 are seen in ventral midbrain dopamine neurons in the mouse. Together, these data suggest that in response to depolarization, dopamine vesicles utilize a cascade of vesicular transporters to dynamically increase the vesicular pH gradient, thereby increasing dopamine vesicle content. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Striatal dopamine release and genetic variation of the serotonin 2C receptor in humans.

    Science.gov (United States)

    Mickey, Brian J; Sanford, Benjamin J; Love, Tiffany M; Shen, Pei-Hong; Hodgkinson, Colin A; Stohler, Christian S; Goldman, David; Zubieta, Jon-Kar

    2012-07-04

    Mesoaccumbal and nigrostriatal projections are sensitive to stress, and heightened stress sensitivity is thought to confer risk for neuropsychiatric disorders. Serotonin 2C (5-HT(2C)) receptors mediate the inhibitory effects of serotonin on dopaminergic circuitry in experimental animals, and preclinical findings have implicated 5-HT(2C) receptors in motivated behaviors and psychotropic drug mechanisms. In humans, a common missense single-nucleotide change (rs6318, Cys23Ser) in the 5-HT(2C) receptor gene (HTR2C) has been associated with altered activity in vitro and with clinical mood disorders. We hypothesized that dopaminergic circuitry would be more sensitive to stress in humans carrying the Ser23 variant. To test this hypothesis, we studied 54 healthy humans using positron emission tomography and the displaceable D(2)/D(3) receptor radiotracer [(11)C]raclopride. Binding potential (BP(ND)) was quantified before and after a standardized stress challenge consisting of 20 min of moderate deep muscular pain, and reduction in BP(ND) served as an index of dopamine release. The Cys23Ser variant was genotyped on a custom array, and ancestry informative markers were used to control for population stratification. We found greater dopamine release in the nucleus accumbens, caudate nucleus, and putamen among Ser23 carriers, after controlling for sex, age, and ancestry. Genotype accounted for 12% of the variance in dopamine release in the nucleus accumbens. There was no association of Cys23Ser with baseline BP(ND). These findings indicate that a putatively functional HTR2C variant (Ser23) is associated with greater striatal dopamine release during pain in healthy humans. Mesoaccumbal stress sensitivity may mediate the effects of HTR2C variation on risk of neuropsychiatric disorders.

  6. The dopamine transporter: role in neurotoxicity and human disease

    International Nuclear Information System (INIS)

    Bannon, Michael J.

    2005-01-01

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  7. The dopamine transporter: role in neurotoxicity and human disease

    Energy Technology Data Exchange (ETDEWEB)

    Bannon, Michael J [Department of Psychiatry and Behavioral Neuroscience, Pharmacology, and Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

    2005-05-01

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  8. Sub-second changes in accumbal dopamine during sexual behavior in male rats.

    Science.gov (United States)

    Robinson, D L; Phillips, P E; Budygin, E A; Trafton, B J; Garris, P A; Wightman, R M

    2001-08-08

    Transient (200--900 ms), high concentrations (200--500 nM) of dopamine, measured using fast-scan cyclic voltammetry, occurred in the nucleus accumbens core of male rats at the presentation of a receptive female. Additional dopamine signals were observed during subsequent approach behavior. Background-subtracted cyclic voltammograms of the naturally-evoked signals matched those of electrically-evoked dopamine measured at the same recording sites. Administration of nomifensine amplified natural and evoked dopamine release, and increased the frequency of detectable signals. While gradual changes in dopamine concentration during sexual behavior have been well established, these findings dramatically improve the time resolution. The observed dopamine transients, probably resulting from neuronal burst firing, represent the first direct correlation of dopamine with sexual behavior on a sub-second time scale.

  9. Tyrosinase-Based Biosensors for Selective Dopamine Detection

    Directory of Open Access Journals (Sweden)

    Monica Florescu

    2017-06-01

    Full Text Available A novel tyrosinase-based biosensor was developed for the detection of dopamine (DA. For increased selectivity, gold electrodes were previously modified with cobalt (II-porphyrin (CoP film with electrocatalytic activity, to act both as an electrochemical mediator and an enzyme support, upon which the enzyme tyrosinase (Tyr was cross-linked. Differential pulse voltammetry was used for electrochemical detection and the reduction current of dopamine-quinone was measured as a function of dopamine concentration. Our experiments demonstrated that the presence of CoP improves the selectivity of the electrode towards dopamine in the presence of ascorbic acid (AA, with a linear trend of concentration dependence in the range of 2–30 µM. By optimizing the conditioning parameters, a separation of 130 mV between the peak potentials for ascorbic acid AA and DA was obtained, allowing the selective detection of DA. The biosensor had a sensitivity of 1.22 ± 0.02 µA·cm−2·µM−1 and a detection limit of 0.43 µM. Biosensor performances were tested in the presence of dopamine medication, with satisfactory results in terms of recovery (96%, and relative standard deviation values below 5%. These results confirmed the applicability of the biosensors in real samples such as human urine and blood serum.

  10. Global pollution monitoring of polychlorinated dibenzo-p-dioxins (PCDDs), furans (PCDFs) and coplanar polychlorinated biphenyls (coplanar PCBs) using skipjack tuna as bioindicator

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Daisuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Watanabe, Mafumi [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Subramanian, Annamalai [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Tanaka, Hiroyuki [National Research Institute of Fisheries and Environment of Inland Sea (Japan); Fillmann, Gilberto [Fundacao Universidade Federal do Rio Grande (Brazil); Lam, Paul K.S. [Department of Biology and Chemistry, City University of Hong Kong, Hong Kong (China); Zheng, Gene J. [Department of Biology and Chemistry, City University of Hong Kong, Hong Kong (China); Muchtar, Muswerry [Research and Development Center for Oceanology, Indonesian Institute of Sciences (Indonesia); Razak, Hamidah [Research and Development Center for Oceanology, Indonesian Institute of Sciences (Indonesia); Prudente, Maricar [Science Education Department, De La Salle University (Philippines); Chung, Kyu-Hyuck [College of Pharmacy, Sungkyunkwan University (Korea, Republic of); Tanabe, Shinsuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan)]. E-mail: shinsuke@agr.ehime-u.ac.jp

    2005-07-15

    In order to elucidate the global distribution of dioxins and related compounds, such as PCDDs, PCDFs and coplanar PCBs, levels of these compounds were determined in the muscle of skipjack tuna (Katsuwonus pelamis) collected from the offshore waters and open seas near Japan, Taiwan, Philippines, Indonesia, Seychelles and Brazil, and the Japan Sea, the East China Sea, the South China Sea, the Indian Ocean and the North Pacific Ocean. PCDDs, PCDFs and coplanar PCBs were detected in almost all the specimens collected from all the locations surveyed, indicating widespread contamination by these compounds in the marine environment. Higher concentrations of dioxins and coplanar PCBs were detected in the samples from temperate Asian regions, plausibly due to larger usage and anthropogenic generation in highly industrialized countries around the East China Sea and the South China Sea, such as Japan, Korea, Taiwan, Hong Kong and coastal China. - Global pollution monitoring of PCDD/Fs and coplanar PCBs in offshore water and open sea were conducted using skipjack tuna as bioindicator.

  11. Global pollution monitoring of polychlorinated dibenzo-p-dioxins (PCDDs), furans (PCDFs) and coplanar polychlorinated biphenyls (coplanar PCBs) using skipjack tuna as bioindicator

    International Nuclear Information System (INIS)

    Ueno, Daisuke; Watanabe, Mafumi; Subramanian, Annamalai; Tanaka, Hiroyuki; Fillmann, Gilberto; Lam, Paul K.S.; Zheng, Gene J.; Muchtar, Muswerry; Razak, Hamidah; Prudente, Maricar; Chung, Kyu-Hyuck; Tanabe, Shinsuke

    2005-01-01

    In order to elucidate the global distribution of dioxins and related compounds, such as PCDDs, PCDFs and coplanar PCBs, levels of these compounds were determined in the muscle of skipjack tuna (Katsuwonus pelamis) collected from the offshore waters and open seas near Japan, Taiwan, Philippines, Indonesia, Seychelles and Brazil, and the Japan Sea, the East China Sea, the South China Sea, the Indian Ocean and the North Pacific Ocean. PCDDs, PCDFs and coplanar PCBs were detected in almost all the specimens collected from all the locations surveyed, indicating widespread contamination by these compounds in the marine environment. Higher concentrations of dioxins and coplanar PCBs were detected in the samples from temperate Asian regions, plausibly due to larger usage and anthropogenic generation in highly industrialized countries around the East China Sea and the South China Sea, such as Japan, Korea, Taiwan, Hong Kong and coastal China. - Global pollution monitoring of PCDD/Fs and coplanar PCBs in offshore water and open sea were conducted using skipjack tuna as bioindicator

  12. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

    International Nuclear Information System (INIS)

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Gore, Andrea C.

    2011-01-01

    Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA B receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation

  13. Influence of phasic and tonic dopamine release on receptor activation

    DEFF Research Database (Denmark)

    Dreyer, Jakob Kristoffer Kisbye; Herrik, Kjartan F; Berg, Rune W

    2010-01-01

    Tonic and phasic dopamine release is implicated in learning, motivation, and motor functions. However, the relationship between spike patterns in dopaminergic neurons, the extracellular concentration of dopamine, and activation of dopamine receptors remains unresolved. In the present study, we...... develop a computational model of dopamine signaling that give insight into the relationship between the dynamics of release and occupancy of D(1) and D(2) receptors. The model is derived from first principles using experimental data. It has no free parameters and offers unbiased estimation...

  14. Effects of in ovo exposure to PCBs (coplanar congener, kanechlor mixture, hydroxylated metabolite) on the developing cell-mediated immunity in chickens

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, J.; Matsuda, M.; Kawano, M.; Wakimoto, T. [Faculty of Agriculture, Ehime Univ., Matsuyama, Ehime (Japan); Kashima, Y. [Dept. of Hygiene, Yokohama City Univ. School of Medicine, Yokohama (Japan)

    2004-09-15

    Polychlorinated biphenyls (PCBs) are wide spread environmental contaminants and known to cause various adverse effects on health of human and wildlife. Immune system is one of the several targets for toxic effects of PCBs and its normal balance is often disrupted by the exposure of the compounds. For example, PCBs may induce immune suppression and result in increased susceptibility to bacterial and viral infections, or conversely, excessive immune enhancement may cause adverse outcomes including as autoimmune disease and anergy. Therefore immune function is regarded as one of an important endpoint in toxicological risk assessment. There are a number of studies shown that neonatal organisms perinatally exposed to polyhalogenated aromatic hydrocarbons (PHAHs) such as PCBs have severer effects on their immune system than adult. Dioxins and coplanar PCB congeners, structurally planar PHAHs are known to have high affinity for aryl hydrocarbon receptor (AhR). 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) have the strongest affinity among such compounds and these are considered to act on immune system through AhR. On the other hand, such as non-planar PCB congeners with low affinity for AhR, which are abundantly contained in commercial PCB preparations have non-additive (antagonistic) effects on immune function. Prenatal exposure of TCDD to rodent induced abnormal lymphoid development in the thymus and thymus-dependent immune functions were remarkably disturbed. Although several experimental studies in mammals have been carried out on the developmental immunotoxicity of PCBs, there are still limited information available on avian species. Thus in this study, prenatal exposure to low level of PCBs and the effects on the developing immune system were investigated with chicken as a model animal of avian species, especially it is focused on the cell-mediated immune function.

  15. Effects of an acute therapeutic or rewarding dose of amphetamine on acquisition of Pavlovian autoshaping and ventral striatal dopamine signaling.

    Science.gov (United States)

    Schuweiler, D R; Athens, J M; Thompson, J M; Vazhayil, S T; Garris, P A

    2018-01-15

    Rewarding doses of amphetamine increase the amplitude, duration, and frequency of dopamine transients in the ventral striatum. Debate continues at the behavioral level about which component of reward, learning or incentive salience, is signaled by these dopamine transients and thus altered in addiction. The learning hypothesis proposes that rewarding drugs result in pathological overlearning of drug-predictive cues, while the incentive sensitization hypothesis suggests that rewarding drugs result in sensitized attribution of incentive salience to drug-predictive cues. Therapeutic doses of amphetamine, such as those used to treat attention-deficit hyperactivity disorder, are hypothesized to enhance the ventral striatal dopamine transients that are critical for reward-related learning and to enhance Pavlovian learning. However, the effects of therapeutic doses of amphetamine on Pavlovian learning are poorly understood, and the effects on dopamine transients are completely unknown. We determined the effects of an acute pre-training therapeutic or rewarding amphetamine injection on the acquisition of Pavlovian autoshaping in the intact rat. We also determined the effects of these doses on electrically evoked transient-like dopamine signals using fast-scan cyclic voltammetry in the anesthetized rat. The rewarding dose enhanced the amplitude and duration of DA signals, caused acute task disengagement, impaired learning for several days, and triggered incentive sensitization. The therapeutic dose produced smaller enhancements in DA signals but did not have similar behavioral effects. These results underscore the necessity of more studies using therapeutic doses, and suggest a hybrid learning/incentive sensitization model may be required to explain the development of addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Thorndike’s Law 2.0: Dopamine and the regulation of thrift

    Directory of Open Access Journals (Sweden)

    Jeff A Beeler

    2012-08-01

    Full Text Available Dopamine is widely associated with reward, motivation and reinforcement learning. Research on dopamine has emphasized its contribution to compulsive behaviors, such as addiction and overeating, with less examination of its potential role in behavioral flexibility in normal, non-pathological states. In the study reviewed here, we investigated the effect of increased tonic dopamine in a two-lever homecage operant paradigm where the relative value of the levers was dynamic, requiring the mice to constantly monitor reward outcome and adapt their behavior. The data were fit to a temporal difference learning model that showed that mice with elevated dopamine exhibited less coupling between reward history and behavioral choice. This work suggests a way to integrate motivational and learning theories of dopamine into a single formal model where tonic dopamine regulates the expression of prior reward learning by controlling the degree to which learned reward values bias behavioral choice. Here I place these results in a broader context of dopamine’s role in instrumental learning and suggest a novel hypothesis that tonic dopamine regulates thrift, the degree to which an animal needs to exploit its prior reward learning to maximize return on energy expenditure. Our data suggest that increased dopamine decreases thriftiness, facilitating energy expenditure and permitting greater exploration. Conversely, this implies that decreased dopamine increases thriftiness, favoring the exploitation of prior reward learning and diminishing exploration. This perspective provides a different window onto the role dopamine may play in behavioral flexibility and its failure, compulsive behavior.

  17. Reduced dopamine transporter binding predates impulse control disorders in Parkinson's disease.

    Science.gov (United States)

    Vriend, Chris; Nordbeck, Anna H; Booij, Jan; van der Werf, Ysbrand D; Pattij, Tommy; Voorn, Pieter; Raijmakers, Pieter; Foncke, Elisabeth M J; van de Giessen, Elsmarieke; Berendse, Henk W; van den Heuvel, Odile A

    2014-06-01

    Impulse control disorders (ICD) are relatively common in Parkinson's disease (PD) and generally are regarded as adverse effects of dopamine replacement therapy, although certain demographic and clinical risk factors are also involved. Previous single-photon emission computed tomography (SPECT) studies showed reduced ventral striatal dopamine transporter binding in Parkinson patients with ICD compared with patients without. Nevertheless, these studies were performed in patients with preexisting impulse control impairments, which impedes clear-cut interpretation of these findings. We retrospectively procured follow-up data from 31 medication-naïve PD patients who underwent dopamine transporter SPECT imaging at baseline and were subsequently treated with dopamine replacement therapy. We used questionnaires and a telephone interview to assess medication status and ICD symptom development during the follow-up period (31.5 ± 12.0 months). Eleven patients developed ICD symptoms during the follow-up period, eight of which were taking dopamine agonists. The PD patients with ICD symptoms at follow-up had higher baseline depressive scores and lower baseline dopamine transporter availability in the right ventral striatum, anterior-dorsal striatum, and posterior putamen compared with PD patients without ICD symptoms. No baseline between-group differences in age and disease stage or duration were found. The ICD symptom severity correlated negatively with baseline dopamine transporter availability in the right ventral and anterior-dorsal striatum. The results of this preliminary study show that reduced striatal dopamine transporter availability predates the development of ICD symptoms after dopamine replacement therapy and may constitute a neurobiological risk factor related to a lower premorbid dopamine transporter availability or a more pronounced dopamine denervation in PD patients susceptible to ICD. © 2014 International Parkinson and Movement Disorder Society.

  18. Temporal and spatial variation of polychlorinated biphenyls (PCBs) contamination in environmental compartments of highly polluted area in Central Russia.

    Science.gov (United States)

    Malina, Natalia; Mazlova, Elena A

    2017-10-01

    This study highlights the fact that serious contamination from polychlorinated biphenyls (PCBs) still exists in Serpukhov City (Russia). The research help to determine the temporal (16- and 24-year periods) and spatial PCBs distribution in the environmental compartments of the studied region. Samples of soil, sediments, water and plants were analysed in order to establish their contamination levels. The most recent data on the Serpukhov City's soil contamination showed that the PCBs concentrations varies from 0.0009 to 1169 mg/kg depending on the sampling point and the distance from the pollution source. The temporal trends of the contamination distribution with the soil depth showed contamination migration in the upper soil layers of the highly polluted site. The high level of water pollution (11.5 μg/L) in the proximity to the contamination source and the sediments contamination (0.098-119 mg/kg) were determined, as well as the water migration pathways of the PCBs that were prevalent in the studied region. The PCB congener group (by the level of chlorination) analysis showed that heptachlorinated biphenyls were only found in the soils in close proximity to the contamination place, while biphenyls with Cl ≤ 6 were found in the soil samples downstream of the condenser plant and with Cl ≤ 5 in the soil samples upstream of the plant. The plant uptake of PCBs, even on the extremely contaminated site, was shown. In turn, this research present new knowledge necessary for the development of a contaminated territory remediation strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Differences between the release of radiolabelled and endogenous dopamine from superfused rat brain slices: effects of depolarizing stimuli, amphetamine and synthesis inhibition

    International Nuclear Information System (INIS)

    Herdon, H.; Strupish, J.; Nahorski, S.R.

    1985-01-01

    Direct comparisons between radiolabelled and endogenous dopamine (DA) release from superfused rat brain slices have been made. Striatal slices were prelabelled with [ 3 H]dopamine ([ 3 H]DA), then superfused at 0.5 ml/min and the released catecholamines analyzed by HPLC with electrochemical detection and radioactivity present in superfusate fractions also counted. The studies indicate that labelled and endogenous amine release do not always occur in parallel, and that major causes of discrepancy between them may include the presence of a large newly-synthesized component in endogenous release and the uneven distribution of labelled amine within endogenous releasable pools. The results also suggest that the prelabelling process itself may alter the pools contributing to subsequent endogenous release. (Auth.)

  20. Regenerative, Highly-Sensitive, Non-Enzymatic Dopamine Sensor and Impact of Different Buffer Systems in Dopamine Sensing

    Directory of Open Access Journals (Sweden)

    Saumya Joshi

    2018-01-01

    Full Text Available Carbon nanotube field-effect transistors are used extensively in ultra-sensitive biomolecule sensing applications. Along with high sensitivity, the possibility of regeneration is highly desired in bio-sensors. An important constituent of such bio-sensing systems is the buffer used to maintain pH and provide an ionic conducting medium, among its other properties. In this work, we demonstrate highly-sensitive regenerative dopamine sensors and the impact of varying buffer composition and type on the electrolyte gated field effect sensors. The role of the buffer system is an often ignored condition in the electrical characterization of sensors. Non-enzymatic dopamine sensors are fabricated and regenerated in hydrochloric acid (HCl solution. The sensors are finally measured against four different buffer solutions. The impact of the nature and chemical structure of buffer molecules on the dopamine sensors is shown, and the appropriate buffer systems are demonstrated.